NeuroMolecular Medicine

, Volume 7, Issue 1–2, pp 157–180 | Cite as

Galanin and its receptors in neurological disorders

  • Linda Lundström
  • Anna Elmquist
  • Tamas Bartfai
  • Ülo Langel
Original Article

Abstract

Galanin is a highly inducible neuropeptide, showing distinct up-regulation after pathological disturbance within the nervous system. Significant increase in galanin expression is observed after peripheral nerve injury, in the basal forebrain in Alzheimer’s disease (AD), during neuronal development, and after stimulation with estrogen, while seizure activity deplete galanin in the hippocampus. A wide distribution of galanin and its receptors is seen in the nervous system, often in co-localization with classical neurotransmitters and other neuromodulators. Galanin acts predominantly as an inhibitory, hyperpolarizing neuromodulator on neurotransmitter and glucose-induced insulin release and stimulates growth hormone and prolactin secretion. Galanin has been implicated in several higher order physiological functions including cognition, feeding, nociception, mood regulation, and neuroendocrine modulation. The effects of galanin are mediated via three G protein-coupled receptors with different functional coupling. Moderate to low pharmacological effects are seen by galanin under physiological conditions, in contrast to its dramatic effects on the nervous system after neuronal disturbance. This pathophysiological heavy function of the galaninergic system renders it an interest for disorders such as AD, depression, and epilepsy in terms of side effects. Some properties of the galaninergic system are of particular importance in the context of neurodegeneration. Galanin is highly inducible, 10- to 100-fold, upon nerve injury, whereas most neuropeptides are induced 1.5- to 2-fold. Galanin is strongly neurotrophic during development as well as subsequent to injury. Whereas other neurotrophic neuropeptides like VIP and PACAP activate cAMP synthesis, galanin suppresses its synthesis, yet it is a strong neurotrophic as well as neuroprotective agent. As we delineate which galanin receptor subtype mediates neuroprotective and neurotrophic effects and which mediates synaptic inhibition, pharmacological use of receptor-selective galaninergic ligands for treatment in neurodegenerative diseases are coming closer.

Index Entries

Galanin galanin receptors neurodegeneration depression epilepsy Alzheimer’s disease (AD) nerve injury inflammation neurotransmitter neurotrophic factor 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahrén B., Arkhammar P., Berggren P. O., and Nilsson T. (1986) Galanin inhibits glucose-stimulated insulin release by a mechanism involving hyperpolarization and lowering of cytoplasmic free Ca2+ concentration. Biochem. Biophys. Res. Commun. 140, 1059–1063.PubMedCrossRefGoogle Scholar
  2. Ahrén B., Pacini G., Wynick D., Wierup N., and Sundler F. (2004) Loss-of-function mutation of the galanin gene is associated with perturbed islet function in mice. Endocrinology 145, 3190–3196.PubMedCrossRefGoogle Scholar
  3. Amoroso D., Girotti P., Fisone G., Bartfai T., and Consolo S. (1992) Mechanism of the galanin induced increase in acetylcholine release in vivo from striata of freely moving rats. Brain Res. 589, 33–38.PubMedCrossRefGoogle Scholar
  4. Anisimov S. V., Tarasov K. V., Riordon D., Wobus A. M., and Boheler K. R. (2002a) SAGE identification of differentiation responsive genes in P19 embryonic cells induced to form cardiomyocytes in vitro. Mech. Dev. 117, 25–74.PubMedCrossRefGoogle Scholar
  5. Anisimov S. V., Tarasov K. V., Tweedie D., Stern M. D., Wobus A. M., and Boheler K. R. (2002b) SAGE identification of gene transcripts with profiles unique to pluripotent mouse R1 embryonic stem cells. Genomics 79, 169–176.PubMedCrossRefGoogle Scholar
  6. Bartfai T., Hökfelt T., and Langel Ü. (1993a) Galanin—a neuroendocrine peptide. Crit. Rev. Neurobiol. 7, 229–274.PubMedGoogle Scholar
  7. Bartfai T., Langel Ü., Bedecs K., et al. (1993b) Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes. Proc. Natl. Acad. Sci. USA 90, 11287–11291.PubMedCrossRefGoogle Scholar
  8. Bartfai T., Lu X., Badie-Mahdavi H., et al. (2004) Galmic, a nonpeptide galanin receptor agonist, affects behaviors in seizure, pain, and forced-swim tests. Proc. Natl. Acad. Sci. USA 101, 10470–10475.PubMedCrossRefGoogle Scholar
  9. Bauer F. E., Ginsberg L., Venetikou M., MacKay D. J., Burrin J. M., and Bloom S. R. (1986) Growth hormone release in man induced by galanin, a new hypothalamic peptide. Lancet 2, 192–195.PubMedCrossRefGoogle Scholar
  10. Beal M. F., MacGarvey U., and Swartz K. J. (1990) Galanin immunoreactivity is increased in the nucleus basalis of Meynertin Alzheimer’s disease. Ann. Neurol. 28, 157–161.PubMedCrossRefGoogle Scholar
  11. Bellido I., Diaz-Cabiale Z., Jimenez-Vasquez P. A., Andbjer B., Mathe A. A., and Fuxe K. (2002) Increased density of galanin binding sites in the dorsal raphe in a genetic rat model of depression. Neurosci. Lett. 317, 101–105.PubMedCrossRefGoogle Scholar
  12. Blakeman K. H., Hao J. X., Xu X. J., et al. (2003) Hyperalgesia and increased neuropathic pain-like response in mice lacking galanin receptor 1 receptors. Neuroscience 117, 221–227.PubMedCrossRefGoogle Scholar
  13. Blakeman K. H., Holmberg K., Hao J. X., et al. (2001) Mice over-expressing galanin have elevated heat nociceptive threshold. Neuroreport 12, 423–425.PubMedCrossRefGoogle Scholar
  14. Borowsky B., Walker M. W., Huang L. Y., et al. (1998) Cloning and characterization of the human galanin GALR2 receptor. Peptides 19, 1771–1781.PubMedCrossRefGoogle Scholar
  15. Bowser R., Kordower J. H., and Mufson E. J. (1997) A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer’s disease. Brain Pathol. 7, 723–730.PubMedGoogle Scholar
  16. Branchek T. A., Smith K. E., Gerald C., and Walker M. W. (2000) Galanin receptor subtypes. Trends Pharmacol. Sci. 21, 109–117.PubMedCrossRefGoogle Scholar
  17. Burgevin M. C., Loquet I., Quarteronet D., and Habert-Ortoli E. (1995) Cloning, pharmacological characterization, and anatomical distribution of a rat cDNA encoding for a galanin receptor. J. Mol. Neurosci. 6, 33–41.PubMedGoogle Scholar
  18. Cai A., Hayes J. D., Patel N., and Hyde J. F. (1999) Targeted overexpression of galanin in lactotrophs of transgenic mice induces hyperprolactinemia and pituitary hyperplasia. Endocrinology 140, 4955–4964.PubMedCrossRefGoogle Scholar
  19. Calza L., Pozza M., Zanni M., Manzini C. U., Manzini E., and Hökfelt T. (1998) Peptide plasticity in primary sensory neurons and spinal cord during adjuvant-induced arthritis in the rat: an immunocytochemical and in situ hybridization study. Neuroscience 82, 575–589.PubMedCrossRefGoogle Scholar
  20. Chan-Palay V. (1988a) Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer’s and Parkinson’s disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J. Comp. Neurol. 273, 543–557.PubMedCrossRefGoogle Scholar
  21. Chan-Palay V. (1988b) Neurons with galanin innervate cholinergic cells in the human basal forebrain and galanin and acetylcholine coexist. Brain Res. Bull. 21, 465–472.PubMedCrossRefGoogle Scholar
  22. Chepurnov S. A., Chepurnova N. E., and Berdiev R. K. (1998) Galanin controls excitability of the brain. Ann. NY. Acad. Sci. 865, 547–550.PubMedCrossRefGoogle Scholar
  23. Ch’ng J. L., Christofides N. D., Anand P., et al. (1985) Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury. Neuroscience 16, 343–354.PubMedCrossRefGoogle Scholar
  24. Collins T., Ginsburg D., Boss J. M., Orkin S. H., and Pober J. S. (1985) Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature 316, 748–750.PubMedCrossRefGoogle Scholar
  25. Consolo S., Baldi G., Russi G., Civenni G., Bartfai T., and Vezzani A. (1994) Impulse flow dependency of galanin release in vivo in the rat ventral hippocampus. Proc. Natl. Acad. Sci. USA 91, 8047–8051.PubMedCrossRefGoogle Scholar
  26. Corness J., Shi T. J., Xu Z. Q., Brulet P., and Hökfelt T. (1996) Influence of leukemia inhibitory factor on galanin/GMAP and neuropeptide Y expression in mouse primary sensory neurons after axotomy. Exp. Brain Res. 112, 79–88.PubMedCrossRefGoogle Scholar
  27. Cortes R., Villar M. J., Verhofstad A., and Hökfelt T. (1990) Effects of central nervous system lesions on the expression of galanin: a comparative in situ hybridization and immunohistochemical study. Proc. Natl. Acad. Sci. USA 87, 7742–7746.PubMedCrossRefGoogle Scholar
  28. Counts S. E., Perez S. E., Ginsberg S. D., De Lacalle S., and Mufson E. J. (2003) Galanin in Alzheimer disease. Mol. Interv. 3, 137–156.PubMedCrossRefGoogle Scholar
  29. Crawley J. N. (1996) Minireview. Galanin-acetylcholine interactions: relevance to memory and Alzheimer’s disease. Life Sci. 58, 2185–2199.PubMedCrossRefGoogle Scholar
  30. Davis T. M., Burrin J. M., and Bloom S. R. (1987) Growth hormone (GH) release in response to GH-releasing hormone in man is 3-fold enhanced by galanin. J. Clin. Endocrinol. Metab. 65, 1248–1252.PubMedGoogle Scholar
  31. de Lacalle S., Kulkarni S., and Mufson E. J. (1997) Plasticity of galaninergic fibers following neurotoxic damage within the rat basal forebrain: initial observations. Exp. Neurol. 146, 361–366.PubMedCrossRefGoogle Scholar
  32. Deecher D. C., Mash D. C., Staley J. K., and Mufson E. J. (1998) Characterization and localization of galanin receptors in human entorhinal cortex. Regul. Pept. 73, 149–159.PubMedCrossRefGoogle Scholar
  33. Degerman A., Chun D., Nguyen T. B., et al. (2002) Local action of estrogen and thyroid hormone on vasoactive intestinal peptide (VIP) and galanin gene expression in the rat anterior pituitary. Neuropeptides 36, 50–57.PubMedCrossRefGoogle Scholar
  34. Diez M., Danner S., Frey P., et al. (2003) Neuropeptide alterations in the hippocampal formation and cortex of transgenic mice overexpressing beta-amyloid precursor protein (APP) with the Swedish double mutation (APP23). Neurobiol. Dis. 14, 579–594.PubMedCrossRefGoogle Scholar
  35. Diez M., Koistinaho J., Kahn K., Games D., and Hökfelt T. (2000) Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein—initial observations. Neuroscience 100, 259–286.PubMedCrossRefGoogle Scholar
  36. Elliott-Hunt C. R., Marsh B., Bacon A., Pope R., Vanderplank P., and Wynick D. (2004) Galanin acts as a neuroprotective factor to the hippocampus. Proc. Natl. Acad. Sci. USA 101, 5105–5110PubMedCrossRefGoogle Scholar
  37. Elvander E., Schott P.A., Sandin J., et al. (2004) Intraseptal muscarinic ligands and galanin: influence on hippocampal acetylcholine and cognition. Neuroscience 126, 541–557.PubMedCrossRefGoogle Scholar
  38. Ericson E. and Ahlenius S. (1999) Suggestive evidence for inhibitory effects of galanin on mesolimbic dopaminergic neurotransmission. Brain Res. 822, 200–209.PubMedCrossRefGoogle Scholar
  39. Fathi Z., Battaglino P. M., et al. (1998) Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor. Brain Res. Mol. Brain Res. 58, 156–169.PubMedCrossRefGoogle Scholar
  40. Fathi Z., Cunningham A. M., Iben L. G., et al. (1997) Cloning, pharmacological characterization and distribution of a novel galanin receptor. Brain. Res. Mol. Brain Res. 51, 49–59.PubMedCrossRefGoogle Scholar
  41. Fetissov S. O., Jacoby A. S., Brumovsky P. R., Shine J., Iismaa T. P., and Hökfelt T. (2003) Altered hippocampal expression of neuropeptides in seizure-prone GALR1 knockout mice. Epilepsia 44, 1022–1033.PubMedCrossRefGoogle Scholar
  42. Finn P. D., Pau K. Y., Spies H. G., Cunningham M. J., Clifton D. K., and Steiner R. A. (2000) Galanin’s functional significance in the regulation of the neuroendocrine reproductive axis of the monkey. Neuroendocrinology 71, 16–26.PubMedCrossRefGoogle Scholar
  43. Fisone G., Bartfai T., Nilsson S., and Hökfelt T. (1991) Galanin inhibits the potassium-evoked release of acetylcholine and the muscarinic receptor-mediated stimulation of phosphoinositide turnover in slices of monkey hippocampus. Brain Res. 568, 279–284.PubMedCrossRefGoogle Scholar
  44. Fisone G., Wu C. F., Consolo S., et al. (1987) Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical, autoradiographic, in vivo, and in vitro studies. Proc. Natl. Acad. Sci. USA 84, 7339–7343.PubMedCrossRefGoogle Scholar
  45. Flatters S. J., Fox A. J., and Dickenson A. H. (2002) Nerve injury induces plasticity that results in spinal inhibitory effects of galanin. Pain 98, 249–258.PubMedCrossRefGoogle Scholar
  46. Florén A., Land T., and Langel Ü. (2000) Galanin receptor subtypes and ligand binding. Neuropeptides 34, 331–337.PubMedCrossRefGoogle Scholar
  47. Fuxe K., Jansson A., Diaz-Cabiale Z., et al. (1998) Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain. Ann. N. Y. Acad. Sci. 863, 274–290.PubMedCrossRefGoogle Scholar
  48. Fuxe K., von Euler G., Agnati L. F., and Ögren S. O. (1988a) Galanin selectively modulates 5-hydroxytryptamine 1A receptors in the rat ventral limbic cortex. Neurosci. Lett. 85, 163–167.PubMedCrossRefGoogle Scholar
  49. Fuxe K., Ögren S. O., Jansson A., Cintra A., Harfstrand A., and Agnati L. F. (1988b) Intraventricular injections of galanin reduces 5-HT metabolism in the ventral limbic cortex, the hippocampal formation and the fronto-parietal cortex of the male rat. Acta. Physiol. Scand. 133, 579–581.PubMedGoogle Scholar
  50. Gabriel S. M., Bierer L. M., Davidson M., Purohit D. P., Perl D. P., and Harotunian V. (1994) Galanin-like immunoreactivity is increased in the postmortem cerebral cortex from patients with Alzheimer’s disease. J. Neurochem. 62, 1516–1523.PubMedCrossRefGoogle Scholar
  51. Gabriel S. M., Kaplan L. M., Martin J. B., and Koenig J. I. (1989) Tissue-specific sex differences in galanin-like immunoreactivity and galanin mRNA during development in the rat. Peptides 10, 369–374.PubMedCrossRefGoogle Scholar
  52. Gentleman S. M., Falkai P., Bogerts B., Herrero M. T., Polak J. M., and Roberts G. W. (1989) Distribution of galanin-like immunoreactivity in the human brain. Brain Res. 505, 311–315.PubMedCrossRefGoogle Scholar
  53. Gomez-Isla T., Price J. L., McKeel D. W., Jr., Morris J. C., Growdon J. H., and Hyman B. T. (1996) Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J. Neurosci. 16, 4491–4500.PubMedGoogle Scholar
  54. Grass S., Jacoby A. S., Iismaa T. P., Crawley J. N., Xu X. J., and Wiesenfeld-Hallin Z. (2003) Flexor reflex excitability in mice lacking galanin receptor galanin-R1. Neurosci. Lett. 345, 153–156.PubMedCrossRefGoogle Scholar
  55. Grenbäck E., Bjellerup P., Wallerman E., et al. (2004) Galanin in pituitary adenomas. Regul. Pept. 117, 127–319.PubMedCrossRefGoogle Scholar
  56. Haberman R. P., Samulski R. J., and McCown T. J. (2003) Attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion. Nat. Med. 9, 1076–1080.PubMedCrossRefGoogle Scholar
  57. Habert-Ortoli E., Amiranoff B., Loquet I., Laburthe M., and Mayaux J. F. (1994) Molecular cloning of a functional human galanin receptor. Proc. Natl. Acad. Sci. USA 91, 9780–9783.PubMedCrossRefGoogle Scholar
  58. Hao J. X., Shi T. J., Xu I. S., et al. (1999) Intrathecal galanin alleviates allodynia-like behaviour in rats after partial peripheral nerve injury. Eur. J. Neurosci. 11, 427–432.PubMedCrossRefGoogle Scholar
  59. Harrison P. S., and Henderson Z. (1999) Quantitative evidence for increase in galanin-immunoreactive terminals in the hippocampal formation following entorhinal cortex lesions in the adult rat. Neurosci. Lett. 266, 41–44.PubMedCrossRefGoogle Scholar
  60. Harro J., and Oreland L. (2001) Depression as a spreading adjustment disorder of monoaminergic neurons: a case for primary implication of the locus coeruleus. Brain Res. Brain Res. Rev. 38, 79–128.PubMedCrossRefGoogle Scholar
  61. Hartonian I., Mufson E. J., and De Lacalle S. (2002) Long-term plastic changes in galanin innervation in the rat basal forebrain. Neuroscience 115, 787–795.PubMedCrossRefGoogle Scholar
  62. Holmes A., Heilig M., Rupniak N. M., Steckler T., and Griebel G. (2003a) Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol. Sci. 24, 580–588.PubMedCrossRefGoogle Scholar
  63. Holmes A., Li Q., Koenig E. A., et al. (2004) Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior. Psychopharmacology (Berl) 178, 276–285.CrossRefGoogle Scholar
  64. Holmes F. E., Bacon A., Pope R. J., et al. (2003b) Transgenic overexpression of galanin in the dorsal root ganglia modulates pain-related behavior. Proc. Natl. Acad. Sci. USA 100, 6180–6185.PubMedCrossRefGoogle Scholar
  65. Holmes F. E., Mahoney S., King V. R., et al. (2000) Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity. Proc. Natl. Acad. Sci. U S A 97, 11563–11568.PubMedCrossRefGoogle Scholar
  66. Hooi S. C., Koenig J. I., Abraczinskas D. R., and Kaplan L. M. (1997) Regulation of anterior pituitary galanin gene expression by thyroid hormone. Brain Res. Mol. Brain Res. 51, 15–22.PubMedCrossRefGoogle Scholar
  67. Hulting A. L., Land T., Berthold M., Langel Ü., Hökfelt T., and Bartfai T. (1993) Galanin receptors from human pituitary tumors assayed with human galanin as ligand. Brain Res. 625, 173–176.PubMedCrossRefGoogle Scholar
  68. Hulting A. L., Meister B., Grimelius L., Wersall J., Änggård A., and Hökfelt T. (1989) Production of a galanin-like peptide by a human pituitary adenoma: immunohistochemical evidence. Acta. Physiol. Scand. 137, 561–562.PubMedCrossRefGoogle Scholar
  69. Husum H., Van Kammen D., Termeer E., Bolwig G., and Mathe A. (2003) Topiramate normalizes hippocampal NPY-LI in flinders sensitive line ‘depressed’ rats and upregulates NPY, galanin, and CRH-LI in the hypothalamus: implications for mood-stabilizing and weight loss-inducing effects. Neuropsychopharmacology 28, 1292–1299.PubMedCrossRefGoogle Scholar
  70. Hygge-Blakeman K., Brumovsky P., Hao J. X., et al. (2004) Galanin over-expression decreases the development of neuropathic pain-like behaviors in mice after partial sciatic nerve injury. Brain Res. 1025, 152–158.PubMedCrossRefGoogle Scholar
  71. Hökfelt T., Millhorn D., Seroogy K., et al. (1987a) Coexistence of peptides with classical neurotransmitters. Experientia 43, 768–780.PubMedCrossRefGoogle Scholar
  72. Hökfelt T., Wiesenfeld-Hallin Z., Villar M., and Melander T. (1987b) Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci. Lett. 83, 217–220.PubMedCrossRefGoogle Scholar
  73. Hökfelt T., Xu Z. Q., Shi T. J., Holmberg K., and Zhang X. (1998) Galanin in ascending systems. Focus on coexistence with 5-hydroxytryptamine and noradrenaline. Ann. N. Y. Acad. Sci. 863, 252–263.PubMedCrossRefGoogle Scholar
  74. Jacobowitz D. M., Kresse A., and Skofitsch G. (2004) Galanin in the brain: chemoarchitectonics and brain cartography—a historical review. Peptides 25, 433–464.PubMedCrossRefGoogle Scholar
  75. Jacoby A. S., Hort Y. J., Constantinescu G., Shine J., and Iismaa T. P. (2002) Critical role for GALR1 galanin receptor in galanin regulation of neuroendocrine function and seizure activity. Brain Res. Mol. Brain Res. 107, 195–200.PubMedCrossRefGoogle Scholar
  76. Jhamandas J. H., Harris K. H., MacTavish D., and Jassar B. S. (2002) Novel excitatory actions of galanin on rat cholinergic basal forebrain neurons: implications for its role in Alzheimer’s disease. J. Neurophysiol. 87, 696–704.PubMedGoogle Scholar
  77. Ji R. R., Zhang Q., Pettersson R. F., and Hökfelt T. (1996) aFGF, bFGF and NGF differentially regulate neuropeptide expression in dorsal root ganglia after axotomy and induce autotomy. Regul. Pept. 66, 179–189.PubMedCrossRefGoogle Scholar
  78. Ji R. R., Zhang X., Zhang Q., et al. (1995) Central and peripheral expression of galanin in response to inflammation. Neuroscience 68, 563–576.PubMedCrossRefGoogle Scholar
  79. Jimenez-Andrade J. M., Zhou S., Du J., et al. (2004) Pro-nociceptive role of peripheral galanin in inflammatory pain. Pain 110, 10–21.PubMedCrossRefGoogle Scholar
  80. Kaplan L. M., Gabriel S. M., Koenig J. I., et al. (1988) Galanin is an estrogen-inducible, secretory product of the rat anterior pituitary. Proc. Natl. Acad. Sci. USA 85, 7408–7412.PubMedCrossRefGoogle Scholar
  81. Kask, K. Berthold M., Bourne J., Andell S., Langel Ü., and Bartfai T. (1995) Binding and agonist/antagonist actions of M35, galanin(1–13)-bradykinin(2–9) amide chimeric peptide, in Rin m 5F insulinoma cells. Regul. Pept. 59, 341–348.PubMedCrossRefGoogle Scholar
  82. Kehr J., Yoshitake T., Wang F. H., et al. (2002) Galanin is a potent in vivo modulator of mesencephalic serotonergic neurotransmission. Neuropsychopharmacology 27, 341–356.PubMedCrossRefGoogle Scholar
  83. Kehr J., Yoshitake T., Wang F. H., et al. (2001) Microdialysis in freely moving mice: determination of acetylcholine, serotonin and noradrenaline release in galanin transgenic mice. J. Neurosci. Methods 109, 71–80.PubMedCrossRefGoogle Scholar
  84. Kerekes N., Landry M., Rydh-Rinder M., and Hökfelt T. (1997) The effect of NGF, BDNF and bFGF on expression of galanin in cultured rat dorsal root ganglia. Brain Res. 754, 131–141.PubMedCrossRefGoogle Scholar
  85. Kerr B. J., Cafferty W. B., Gupta Y. K., et al. (2000a) Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury. Eur. J. Neurosci. 12, 793–802.PubMedCrossRefGoogle Scholar
  86. Kerr B. J., Gupta Y., Pope R., Thompson S. W., Wynick D., and McMahon S. B. (2001) Endogenous galanin potentiates spinal nociceptive processing following inflammation. Pain 93, 267–277.PubMedCrossRefGoogle Scholar
  87. Kerr B. J., Wynick D., Thompson S. W., and McMahon S. B. (2000b) The biological role of galanin in normal and neuropathic states. Prog. Brain Res. 129, 219–230.PubMedCrossRefGoogle Scholar
  88. Kinney G. A., Emmerson P. J., and Miller R. J. (1998) Galanin receptor-mediated inhibition of glutamate release in the arcuate nucleus of the hypothalamus. J. Neurosci. 18, 3489–3500.PubMedGoogle Scholar
  89. Kinney J. W., Barr A. M., Conti B., Behrens M., and Bartfai T. (2004) Society for Neuroscience, San Diego, USA.Google Scholar
  90. Kokaia M., Holmberg K., Nanobashvili A., et al. (2001) Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin. Proc. Natl. Acad. Sci. USA 98, 14006–14011.PubMedCrossRefGoogle Scholar
  91. Kolakowski L. F., Jr., O’Neill G. P., Howard A. D., et al. (1998) Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. J. Neurochem. 71, 2239–2251.PubMedCrossRefGoogle Scholar
  92. Kordower J. H., Chu Y., Stebbins G. T., et al. (2001) Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann. Neurol. 49, 202–213.PubMedCrossRefGoogle Scholar
  93. Kordower J. H., Le H. K., and Mufson E. J. (1992) Galanin immunoreactivity in the primate central nervous system. J. Comp. Neurol. 319, 479–500.PubMedCrossRefGoogle Scholar
  94. Koshiyama H., Kato Y., Inoue T., et al. (1987) Central galanin stimulates pituitary prolactin secretion in rats: possible involvement of hypothalamic vasoactive intestinal polypeptide. Neurosci. Lett. 75, 49–54.PubMedCrossRefGoogle Scholar
  95. Kowall N. W. and Beal M. F. (1989) Galanin-like immunoreactivity is present in human substantia innominata and in senile plaques in Alzheimer’s disease. Neurosci. Lett. 98, 118–213.PubMedCrossRefGoogle Scholar
  96. Lamour Y., Senut M. C., Dutar P., and Bassant M. H. (1988) Neuropeptides and septo-hippocampal neurons: electrophysiological effects and distributions of immunoreactivity. Peptides 9, 1351–1359.PubMedCrossRefGoogle Scholar
  97. Landry M., Holmberg K., Zhang X., and Hökfelt T. (2000) Effect of axotomy on expression of NPY, galanin, and NPY Y1 and Y2 receptors in dorsal root ganglia and the superior cervical ganglion studied with double-labeling in situ hybridization and immunohistochemistry. Exp. Neurol. 162, 361–384.PubMedCrossRefGoogle Scholar
  98. Lang R., Berger A., Hermann A., and Kofler B. (2001) Biphasic response to human galanin of extracellular acidification in human Bowes melanoma cells. Eur. J. Pharmacol. 423, 135–141.PubMedCrossRefGoogle Scholar
  99. Laplante F., Crawley J. N., and Quirion R. (2004) Selective reduction in ventral hippocampal acetylcholine release in awake galanin-treated rats and galanin-overexpressing transgenic mice. Regul. Pept. 122, 91–98.PubMedCrossRefGoogle Scholar
  100. Leung B., Iisma T. P., Leung K. C., Hort Y. J., Turner J., Sheehy J. P., et al. (2002) Galanin in human pituitary adenomas: frequency and clinical significance. Clin. Endocrinol. (Oxf). 56, 397–403.CrossRefGoogle Scholar
  101. Lin E. J., Richichi C., Young D., Baer K., Vezzani A., and During M. J. (2003) Recombinant AAV-mediated expression of galanin in rat hippocampus suppresses seizure development. Eur. J. Neurosci. 18, 2087–2092.PubMedCrossRefGoogle Scholar
  102. Liu H. X., Brumovsky P., Schmidt R., et al. (2001) Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: selective actions via GalR1 and GalR2 receptors. Proc. Natl. Acad. Sci. USA 98, 9960–9964.PubMedCrossRefGoogle Scholar
  103. Liu H. X. and Hökfelt T. (2002) The participation of galanin in pain processing at the spinal level. Trends. Pharmacol. Sci. 23, 468–474.PubMedCrossRefGoogle Scholar
  104. Lu X., Barr A. M., Kinney J. W., et al. (2005) A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus. Proc. Natl. Acad. Sci. USA. 102, 874–879.PubMedCrossRefGoogle Scholar
  105. Lundström L., Sollenberg U., Brewer A., et al. (2004) A Galanin Receptor subtype 1 Specific Agonist. Int. J. Peptide Res. Ther. 11, 17–27.CrossRefGoogle Scholar
  106. Ma W. and Bisby M. A. (1997) Differential expression of galanin immunoreactivities in the primary sensory neurons following partial and complete sciatic nerve injuries. Neuroscience 79, 1183–1195.PubMedCrossRefGoogle Scholar
  107. Ma X., Tong Y. G., Schmidt R., et al. (2001) Effects of galanin receptor agonists on locus coeruleus neurons. Brain Res. 919, 169–174.PubMedCrossRefGoogle Scholar
  108. Mahoney S. A., Hosking R., Farrant S., et al. (2003) The second galanin receptor GalR2 plays a key role in neurite outgrowth from adult sensory neurons. J. Neurosci. 23, 416–421.PubMedGoogle Scholar
  109. Maiter D. M., Hooi S. C., Koenig J. I., and Martin J. B. (1990) Galanin is a physiological regulator of spontaneous pulsatile secretion of growth hormone in the male rat. Endocrinology 126, 1216–1222.PubMedGoogle Scholar
  110. Marti E., Gibson S. J., Polak J. M., et al. (1987) Ontogeny of peptide- and amine-containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia, and rat skin. J. Comp. Neurol. 266, 332–359.PubMedCrossRefGoogle Scholar
  111. Mazarati A., Langel Ü., and Bartfai T. (2001) Galanin: an endogenous anticonvulsant? Neuroscientist 7, 506–517.PubMedGoogle Scholar
  112. Mazarati A., Lu X., Kilk K., Langel Ü., Wasterlain C., and Bartfai T. (2004a) Galanin type 2 receptors regulate neuronal survival, susceptibility to seizures and seizure-induced neurogenesis in the dentate gyrus. Eur. J. Neurosci. 19, 3235–3244.PubMedCrossRefGoogle Scholar
  113. Mazarati A., Lu X., Shinmei S., Badie-Mahdavi H., and Bartfai T. (2004b) Patterns of seizures, hippocampal injury and neurogenesis in three models of status epilepticus in galanin receptor type 1 (GalR1) knockout mice. Neuroscience 128, 431–441.PubMedCrossRefGoogle Scholar
  114. Mazarati A. and Wasterlain C. G. (2002) Anticonvulsant effects of four neuropeptides in the rat hippocampus during self-sustaining status epilepticus. Neurosci. Lett. 331, 123–127.PubMedCrossRefGoogle Scholar
  115. Mazarati A. M., Halaszi E., and Telegdy G. (1992) Anticonvulsive effects of galanin administered into the central nervous system upon the picrotoxin-kindled seizure syndrome in rats. Brain Res. 589, 164–166.PubMedCrossRefGoogle Scholar
  116. Mazarati A. M., Hohmann J. G., Bacon A., et al. (2000) Modulation of hippocampal excitability and seizures by galanin. J. Neurosci. 20, 6276–6281.PubMedGoogle Scholar
  117. Mazarati A. M., Liu H., Soomets U., et al. (1998) Galanin modulation of seizures and seizure modulation of hippocampal galanin in animal models of status epilepticus. J. Neurosci. 18, 10070–10077.PubMedGoogle Scholar
  118. Melander T., Hökfelt T., and Rökaeus A. (1986a) Distribution of galaninlike immunoreactivity in the rat central nervous system. J. Comp. Neurol. 248, 475–517.PubMedCrossRefGoogle Scholar
  119. Melander T., Hökfelt T., Rökaeus A., et al. (1986b) Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS. J. Neurosci. 6, 3640–3654.PubMedGoogle Scholar
  120. Melander T., Staines W. A., Hökfelt T., et al. (1985) Galanin-like immunoreactivity in cholinergic neurons of the septum-basal forebrain complex projecting to the hippocampus of the rat. Brain Res. 360, 130–138.PubMedCrossRefGoogle Scholar
  121. Melander T., Staines W. A., and Rokaeus A. (1986c) Galanin-like immunoreactivity in hippocampal afferents in the rat, with special reference to cholinergic and noradrenergic inputs. Neuroscience 19, 223–240.PubMedCrossRefGoogle Scholar
  122. Mennicken F., Hoffert C., Pelletier M., Ahmad S., and O’Donnell D. (2002) Restricted distribution of galanin receptor 3 (GalR3) mRNA in the adult rat central nervous system. J. Chem. Neuroanat. 24, 257–268.PubMedCrossRefGoogle Scholar
  123. Mercer E. H., Hoyle G. W., Kapur R. P., Brinster R. L., and Palmiter R. D. (1991) The dopamine beta-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice. Neuron 7, 703–716.PubMedCrossRefGoogle Scholar
  124. Mufson E. J., Bothwell M., and Kordower J. H. (1989) Loss of nerve growth factor receptor-containing neurons in Alzheimer’s disease: a quantitative analysis across subregions of the basal forebrain. Exp. Neurol. 105, 221–232.PubMedCrossRefGoogle Scholar
  125. Mufson E. J., Cochran E., Benzing W., and Kordower J. H. (1993) Galaninergic innervation of the cholinergic vertical limb of the diagonal band (Ch2) and bed nucleus of the stria terminalis in aging, Alzheimer’s disease and Down’s syndrome. Dementia 4, 237–250.PubMedGoogle Scholar
  126. Mufson E. J., Deecher D. C., Basile M., Izenwasse S., and Mash D. C. (2000) Galanin receptor plasticity within the nucleus basalis in early and late Alzheimer’s disease: an in vitro autoradiographic analysis. Neuropharmacology 39, 1404–1412.PubMedCrossRefGoogle Scholar
  127. Murakami Y., Kato Y., Koshiyama H., Inoue T., Yanaihara N., and Imura H. (1987) Galanin stimulates growth hormone (GH) secretion via GH-releasing factor (GRF) in conscious rats. Eur. J. Pharmacol. 136, 415–418.PubMedCrossRefGoogle Scholar
  128. Murck H., Antonijevic I. A., Frieboes R. M., Maier P., Schier T., and Steiger A. (1999) Galanin has REM-sleep deprivation-like effects on the sleep EEG in healthy young men. J. Psychiatr. Res. 33, 225–232.PubMedCrossRefGoogle Scholar
  129. Murck H., Held K., Ziegenbein M., Kunzel H., Holsboer F., and Steiger A. (2004) Intravenous administration of the neuropeptide galanin has fast antidepressant efficacy and affects the sleep EEG. Psychoneuroendocrinology 29, 1205–1211.PubMedCrossRefGoogle Scholar
  130. Nahin R. L., Ren K., De Leon M., and Ruda M. (1994) Primary sensory neurons exhibit altered gene expression in a rat model of neuropathic pain. Pain 58, 95–108.PubMedCrossRefGoogle Scholar
  131. Nordström O., Melander T., Hökfelt T., Bartfai T., and Goldstein M. (1987) Evidence for an inhibitory effect of the peptide galanin on dopamine release from the rat median eminence. Neurosci. Lett. 73, 21–26.PubMedCrossRefGoogle Scholar
  132. O’Donnell D., Ahmad S., Wahlestedt C., and Walker P. (1999) Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1. J. Comp. Neurol. 409, 469–481.PubMedCrossRefGoogle Scholar
  133. Ohtaki T., Kumano S., Ishibashi Y., et al. (1999) Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus. J. Biol. Chem. 274, 37041–37045.PubMedCrossRefGoogle Scholar
  134. O’Meara G., Coumis U., Ma S. Y., et al. (2000) Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons. Proc. Natl. Acad. Sci. USA 97, 11569–11574.PubMedCrossRefGoogle Scholar
  135. Ottlecz A., Samson W. K., and McCann S. M. (1986) Galanin: evidence for a hypothalamic site of action to release growth hormone. Peptides 7, 51–53.PubMedCrossRefGoogle Scholar
  136. Ottlecz A., Snyder G. D., and McCann S. M. (1988) Regulatory role of galanin in control of hypothalamic-anterior pituitary function. Proc. Natl. Acad. Sci. USA 85, 9861–9865.PubMedCrossRefGoogle Scholar
  137. Parker E. M., Izzarelli D. G., Nowak H. P., et al. (1995) Cloning and characterization of the rat GALR1 galanin receptor from Rin14B insulinoma cells. Brain Res. Mol. Brain Res. 34, 179–189.PubMedCrossRefGoogle Scholar
  138. Perez S., Basile M., Mash D. C., and Mufson E. J. (2002) Galanin receptor over-expression within the amygdala in early Alzheimer’s disease: an in vitro autoradiographic analysis. J. Chem. Neuroanat. 24, 109–116.PubMedCrossRefGoogle Scholar
  139. Perez S. E., Wynick D., Steiner R. A., and Mufson E. J. (2001) Distribution of galaninergic immunoreactivity in the brain of the mouse. J. Comp. Neurol. 434, 158–185.PubMedCrossRefGoogle Scholar
  140. Perumal P. and Vrontakis M. E. (2003) Transgenic mice over-expressing galanin exhibit pituitary adenomas and increased secretion of galanin, prolactin and growth hormone. J. Endocrinol. 179, 145–154.PubMedCrossRefGoogle Scholar
  141. Pieribone V. A., Xu Z. Q., Zhang X., Grillner S., Bartfai T., and Hökfelt T. (1995) Galanin induces a hyperpolarization of norepinephrine-containing locus coeruleus neurons in the brainstem slice. Neuroscience 64, 861–874.PubMedCrossRefGoogle Scholar
  142. Planas B., Kolb P. E., Raskind M. A., and Miller M. A. (1997) Nerve growth factor induces galanin gene expression in the rat basal forebrain: implications for the treatment of cholinergic dysfunction. J. Comp. Neurol. 379, 563–570.PubMedCrossRefGoogle Scholar
  143. Pooga M., Soomets U., Hällbrink M., et al. (1998) Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat. Biotechnol. 16, 857–861.PubMedCrossRefGoogle Scholar
  144. Pramanik A., and Ögren S. O. (1993) Galanin stimulates striatal acetylcholine release via a mechanism unrelated to cholinergic receptor stimulation. Regul. Pept. 45, 353–362.PubMedCrossRefGoogle Scholar
  145. Puar M. S., Barrabee E., Hallade M., and Patel M. (2000) Sch 420789: a novel fungal metabolite with phospholipase D inhibitory activity. J. Antibiot. (Tokyo) 53, 837–838.Google Scholar
  146. Razani H., Diaz-Cabiale Z., Fuxe K., and Ögren S. O. (2000) Intraventricular galanin produces a time-dependent modulation of 5-HT1A receptors in the dorsal raphe of the rat. Neuroreport 11, 3943–3948.PubMedCrossRefGoogle Scholar
  147. Rodriguez-Puertas R., Nilsson S., Pascual J., Pazos A., and Hökfelt T. (1997) 125I-galanin binding sites in Alzheimer’s disease: increases in hippocampal subfields and a decrease in the caudate nucleus. J. Neurochem. 68, 1106–1113.PubMedCrossRefGoogle Scholar
  148. Rökaeus A., Melander T., Hökfelt T., Lundberg J. M., Tatemoto K., Carlquist M., et al. (1984) A galanin-like peptide in the central nervous system and intestine of the rat. Neurosci. Lett. 47, 161–166.PubMedCrossRefGoogle Scholar
  149. Saar K., Mazarati A. M., Mahlapuu R., et al. (2002) Anticonvulsant activity of a nonpeptide galanin receptor agonist. Proc. Natl. Acad. Sci. USA 99, 7136–7141.PubMedCrossRefGoogle Scholar
  150. Sahu A., Crowley W. R., Tatemoto K., Balasubramaniam A., and Kalra S. P. (1987) Effects of neuropeptide Y, NPY analog (norleucine4-NPY), galanin and neuropeptide K on LH release in ovariectomized (ovx) and ovx estrogen, progesterone-treated rats. Peptides 8, 921–926.PubMedCrossRefGoogle Scholar
  151. Sakurai E., Maeda T., Kaneko S., Akaike A., and Satoh M. (1996) Galanin inhibits long-term potentiation at Schaffer collateral-CA1 synapses in guinea-pig hippocampal slices. Neurosci. Lett. 212, 21–24.PubMedCrossRefGoogle Scholar
  152. Sano T., Vrontakis M. E., Kovacs K., Asa S. L., and Friesen H. G. (1991) Galanin immunoreactivity in neuroendocrine tumors. Arch. Pathol. Lab. Med. 115, 926–929.PubMedGoogle Scholar
  153. Sargent P. A., Kjaer K. H., Bench C. J., et al. (2000) Brain serotonin 1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch. Gen. Psychiatry 57, 174–180.PubMedCrossRefGoogle Scholar
  154. Scott M. K., Ross T. M., Lee D. H., et al. (2000) 2,3-Dihydro-dithiin and -dithiepine-1,1,4,4-tetroxides: small molecule non-peptide antagonists of the human galanin hGAL-1 receptor. Bioorg. Med. Chem. 8, 1383–1391.PubMedCrossRefGoogle Scholar
  155. Seutin V., Verbanck P., Massotte L., and Dresse A. (1989) Galanin decreases the activity of locus coeruleus neurons in vitro. Eur. J. Pharmacol. 164, 373–376.PubMedCrossRefGoogle Scholar
  156. Sevcik J., Finta E. P., and Illes P. (1993) Galanin receptors inhibit the spontaneous firing of locus coeruleus neurones and interact with mu-opioid receptors. Eur. J. Pharmacol. 230, 223–230.PubMedCrossRefGoogle Scholar
  157. Simmons D. R., Spike R. C., and Todd A. J. (1995) Galanin is contained in GABAergic neurons in the rat spinal dorsal horn. Neurosci. Lett. 187, 119–122.PubMedCrossRefGoogle Scholar
  158. Skofitsch G. and Jacobowitz D. M. (1985a) Galanin-like immunoreactivity in capsaicin sensitive sensory neurons and ganglia. Brain Res. Bull. 15, 191–195.PubMedCrossRefGoogle Scholar
  159. Skofitsch G. and Jacobowitz D. M. (1985b) Immunohistochemical mapping of galanin-like neurons in the rat central nervous system. Peptides 6, 509–546.PubMedCrossRefGoogle Scholar
  160. Skofitsch G. and Jacobowitz D. M. (1986a) Quantitative distribution of galanin-like immunoreactivity in the rat central nervous system. Peptides 7, 609–613.PubMedCrossRefGoogle Scholar
  161. Skofitsch G., Sills M. A., and Jacobowitz D. M. (1986b) Autoradiographic distribution of 125I-galanin binding sites in the rat central nervous system. Peptides 7, 1029–1042.PubMedCrossRefGoogle Scholar
  162. Smith K. E., Forray C., Walker M. W., et al. (1997) Expression cloning of a rat hypothalamic galanin receptor coupled to phosphoinositide turnover. J. Biol. Chem. 272, 24612–26616.PubMedCrossRefGoogle Scholar
  163. Smith K. E., Walker M. W., Artymyshyn R., et al. (1998) Cloned human and rat galanin GALR3 receptors. Pharmacology and activation of G-protein inwardly rectifying K+ channels. J. Biol. Chem. 273, 23321–23326.PubMedCrossRefGoogle Scholar
  164. Steiner R. A., Hohmann J. G., Holmes A., et al. (2001) Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 98, 4184–4189.PubMedCrossRefGoogle Scholar
  165. Sten Shi T. J., Zhang X., Holmberg K., Xu Z. Q., and Hökfelt T. (1997) Expression and regulation of galanin-R2 receptors in rat primary sensory neurons: effect of axotomy and inflammation. Neurosci. Lett. 237, 57–60.PubMedCrossRefGoogle Scholar
  166. Sukumaran M., Waxman S. G., Wood J. N., and Pachnis V. (2001) Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c-ret, directs lac Z (beta-galactosidase) expression in developing somatosensory system. Dev. Dyn. 222, 389–402.PubMedCrossRefGoogle Scholar
  167. Tatemoto K., Rökaeus A., Jörnvall H., McDonald T. J., and Mutt V. (1983) Galanin — a novel biologically active peptide from porcine intestine. FEBS Lett. 164, 124–128.PubMedCrossRefGoogle Scholar
  168. Toppila J., Stenberg D., Alanko L., et al. (1995) REM sleep deprivation induces galanin gene expression in the rat brain. Neurosci. Lett. 183, 171–174.PubMedCrossRefGoogle Scholar
  169. Walker L. C., Rance N. E., Price D. L., and Young W. S., 3rd (1991) Galanin mRNA in the nucleus basalis of Meynert complex of baboons and humans. J. Comp. Neurol. 303, 113–120.PubMedCrossRefGoogle Scholar
  170. Wang H. Y., Wild K. D., Shank R. P., and Lee D. H. (1999) Galanin inhibits acetylcholine release from rat cerebral cortex via a pertussis toxin-sensitive G(i)protein. Neuropeptides 33, 197–205.PubMedCrossRefGoogle Scholar
  171. Wang R., Guo W., Ossipov M. H., Vanderah T. W., Porreca F., and Lai J. (2003) Glial cell line-derived neurotrophic factor normalizes neurochemical changes in injured dorsal root ganglion neurons and prevents the expression of experimental neuropathic pain. Neuroscience 121, 815–824.PubMedCrossRefGoogle Scholar
  172. Wang S., Hashemi T., Fried S., Clemmons A. L., and Hawes B. E. (1998) Differential intracellular signaling of the GalR1 and GalR2 galanin receptor subtypes. Biochemistry 37, 6711–6717.PubMedCrossRefGoogle Scholar
  173. Wang S., Hashemi T., He C., Strader C., and Bayne M. (1997a) Molecular cloning and pharmacological characterization of a new galanin receptor subtype. Mol. Pharmacol. 52, 337–343.PubMedGoogle Scholar
  174. Wang S., He C., Hashemi T., and Bayne M. (1997b) Cloning and expressional characterization of a novel galanin receptor. Identification of different pharmacophores within galanin for the three galanin receptor subtypes. J. Biol. Chem. 272, 31949–31952.PubMedCrossRefGoogle Scholar
  175. Weiss J. M., Bonsall R. W., Demetrikopoulos M. K., Emery M. S., and West C. H. (1998) Galanin: a significant role in depression? Ann. N Y. Acad. Sci. 863, 364–382.PubMedCrossRefGoogle Scholar
  176. Vereecken T. H., Vogels O. J., and Nieuwenhuys R. (1994) Neuron loss and shrinkage in the amygdala in Alzheimer’s disease. Neurobiol. Aging 15, 45–54.PubMedCrossRefGoogle Scholar
  177. Wiesenfeld-Hallin Z., Villar M. J., and Hökfelt T. (1989) The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. Brain Res. 486, 205–213.PubMedCrossRefGoogle Scholar
  178. Wiesenfeld-Hallin Z., Xu X. J., Langel Ü., Bedecs K., Hökfelt T., and Bartfai T. (1992) Galanin-mediated control of pain: enhanced role after nerve injury. Proc. Natl. Acad. Sci. USA 89, 3334–3337.PubMedCrossRefGoogle Scholar
  179. Wiesenfeld-Hallin Z., Xu X. J., Villar M. J., and Hökfelt T. (1990) Intrathecal galanin potentiates the spinal analgesic effect of morphine: electrophysiological and behavioural studies. Neurosci. Lett. 109, 217–221.PubMedCrossRefGoogle Scholar
  180. Villar M. J., Cortes R., Theodorsson E., et al. (1989) Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin. Neuroscience 33, 587–604.PubMedCrossRefGoogle Scholar
  181. Villar M. J., Meister B., Cortes R., Schalling M., Morris M., and Hökfelt T. (1990) Neuropeptide gene expression in hypothalamic magnocellular neurons of normal and hypophysectomized rats: a combined immunohistochemical and in situ hybridization study. Neuroscience 36, 181–199.PubMedCrossRefGoogle Scholar
  182. Villar M. J., Wiesenfeld-Hallin Z., Xu X. J., Theodorsson E., Emson P. C., and Hökfelt T. (1991) Further studies on galanin-, substance P-, and CGRP-like immunoreactivities in primary sensory neurons and spinal cord: effects of dorsal rhizotomies and sciatic nerve lesions. Exp. Neurol. 112, 29–39.PubMedCrossRefGoogle Scholar
  183. Wittau N., Grosse R., Kalkbrenner F., Gohla A., Schultz G., and Gudermann T. (2000) The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins. Oncogene 19, 4199–4209.PubMedCrossRefGoogle Scholar
  184. Vogels O. J., Broere C. A., ter Laak H. J., ten Donkelaar H. J., Nieuwenhuys R., and Schulte B. P. (1990) Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer’s disease. Neurobiol. Aging 11, 3–13.PubMedCrossRefGoogle Scholar
  185. Wrenn C. C., and Crawley J. N. (2001) Pharmacological evidence supporting a role for galanin in cognition and affect. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 283–299.PubMedCrossRefGoogle Scholar
  186. Wrenn C. C., Kinney J. W., Marriott L. K., et al. (2004) Learning and memory performance in mice lacking the GAL-R1 subtype of galanin receptor. Eur. J. Neurosci. 19, 1384–1396.PubMedCrossRefGoogle Scholar
  187. Vrontakis M. E., Sano T., Kovacs K., and Friesen H. G. (1990) Presence of galanin-like immunoreactivity in nontumorous corticotrophs and corticotroph adenomas of the human pituitary. J. Clin. Endocrinol. Metab. 70, 747–751.PubMedCrossRefGoogle Scholar
  188. Vrontakis M. E., Yamamoto T., Schroedter I. C., Nagy J. I., and Friesen H. G. (1989) Estrogen induction of galanin synthesis in the rat anterior pituitary gland demonstrated by in situ hybridization and immunohistochemistry. Neurosci. Lett. 100, 59–64.PubMedCrossRefGoogle Scholar
  189. Wynick D., Small C. J., Bacon A., et al. (1998) Galanin regulates prolactin release and lactotroph proliferation. Proc. Natl. Acad. Sci. USA 95, 12671–12676.PubMedCrossRefGoogle Scholar
  190. Xu I. S., Grass S., Xu X. J., and Wiesenfeld-Hallin Z. (1998a) On the role of galanin in mediating spinal flexor reflex excitability in inflammation. Neuroscience 85, 827–835.PubMedCrossRefGoogle Scholar
  191. Xu S., Zhang Y., Lundeberg T., and Yu L. (2000a) Effects of galanin on wide-dynamic range neuron activity in the spinal dorsal horn of rats with sciatic nerve ligation. Regul. Pept. 95, 19–23.PubMedCrossRefGoogle Scholar
  192. Xu X. J., Hökfelt T., Bartfai T., and Wiesenfeld-Hallin Z. (2000b) Galanin and spinal nociceptive mechanisms: recent advances and therapeutic implications. Neuropeptides 34, 137–147.PubMedCrossRefGoogle Scholar
  193. Xu X. J., Wiesenfeld-Hallin Z., and Hökfelt T. (1991) Intrathecal galanin blocks the prolonged increase in spinal cord flexor reflex excitability induced by conditioning stimulation of unmyelinated muscle afferents in the rat. Brain Res. 541, 350–353.PubMedCrossRefGoogle Scholar
  194. Xu X. J., Wiesenfeld-Hallin Z., Villar M. J., Fahrenkrug J., and Hökfelt T. (1990) On the Role of Galanin, Substance P and Other Neuropeptides in Primary Sensory Neurons of the Rat: Studies on Spinal Reflex Excitability and Peripheral Axotomy. Eur. J. Neurosci. 2, 733–743.PubMedCrossRefGoogle Scholar
  195. Xu Z. Q., Bartfai T., Langel Ü., and Hökfelt T. (1998b) Effects of three galanin analogs on the outward current evoked by galanin in locus coeruleus. Ann. NY. Acad. Sci. 863, 459–465.PubMedCrossRefGoogle Scholar
  196. Xu Z. Q., and Hökfelt T. (1997) Expression of galanin and nitric oxide synthase in subpopulations of serotonin neurons of the rat dorsal raphe nucleus. J. Chem. Neuroanat. 13, 169–187.PubMedCrossRefGoogle Scholar
  197. Xu Z. Q., Shi T. J., and Hökfelt T. (1996a) Expression of galanin and a galanin receptor in several sensory systems and bone anlage of rat embryos. Proc. Natl. Acad. Sci. USA 93, 14901–14905.PubMedCrossRefGoogle Scholar
  198. Xu Z. Q., Shi T. J., and Hökfelt T. (1998c) Galanin/GMAP-and NPY-like immunoreactivities in locus coeruleus and noradrenergic nerve terminals in the hippocampal formation and cortex with notes on the galanin-R1 and -R2 receptors. J. Comp. Neurol. 392, 227–251.PubMedCrossRefGoogle Scholar
  199. Xu Z. Q., Shi T. J., Landry M., and Hökfelt T. (1996b) Evidence for galanin receptors in primary sensory neurones and effect of axotomy and inflammation. Neuroreport 8, 237–242.PubMedCrossRefGoogle Scholar
  200. Xu Z. Q., Zhang X., Pieribone V. A., Grillner S., and Hökfelt T. (1998d) Galanin-5-hydroxytryptamine interactions: electrophysiological, immunohistochemical and in situ hybridization studies on rat dorsal raphe neurons with a note on galanin R1 and R2 receptors. Neuroscience 87, 79–94.PubMedCrossRefGoogle Scholar
  201. Yoshida M., Yokoo H., Tanaka T., Emoto H., and Tanaka M. (1994) Opposite changes in the mesolimbic dopamine metabolism in the nerve terminal and cell body sites induced by locally infused baclofen in the rat. Brain Res. 636, 111–114.PubMedCrossRefGoogle Scholar
  202. Yoshitake T., Reenila I., Ögren S. O., Hökfelt T., and Kehr J. (2003a) Galanin attenuates basal and antidepressant drug-induced increase of extracellular serotonin and noradrenaline levels in the rat hippocampus. Neurosci. Lett. 339, 239–242.PubMedCrossRefGoogle Scholar
  203. Yoshitake T., Wang F. H., Kuteeva E., et al. (2004) Enhanced hippocampal noradrenaline and serotonin release in galanin-overexpressing mice after repeated forced swimming test. Proc. Natl. Acad. Sci. USA 101, 354–359.PubMedCrossRefGoogle Scholar
  204. Yoshitake T., Yoshitake S., Yamaguchi M., Ögren S. O., and Kehr J. (2003b) Activation of 5-HT(1A) autoreceptors enhances the inhibitory effect of galanin on hippocampal 5-HT release in vivo. Neuropharmacology 44, 206–213.PubMedCrossRefGoogle Scholar
  205. Zachariou V., Brunzell D. H., Hawes J., et al. (2003) The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal. Proc. Natl. Acad. Sci. USA 100, 9028–9033.PubMedCrossRefGoogle Scholar
  206. Zachariou V., Georgescu D., Kansal L., Merriam P., and Picciotto M. R. (2001) Galanin receptor 1 gene expression is regulated by cyclic AMP through a CREB-dependent mechanism. J. Neurochem. 76, 191–200.PubMedCrossRefGoogle Scholar
  207. Zhang X., Bean A. J., Wiesenfeld-Hallin Z., Xu X. J., and Hökfelt T. (1995a) Ultrastructural studies on peptides in the dorsal horn of the rat spinal cord—III. Effects of peripheral axotomy with special reference to galanin. Neuroscience 64, 893–915.PubMedCrossRefGoogle Scholar
  208. Zhang X., Ju G., Elde R., and Hökfelt T. (1993a) Effect of peripheral nerve cut on neuropeptides in dorsal root ganglia and the spinal cord of monkey with special reference to galanin. J. Neurocytol. 22, 342–381.PubMedCrossRefGoogle Scholar
  209. Zhang X., Nicholas A. P., and Hökfelt T. (1993b) Ultrastructural studies on peptides in the dorsal horn of the spinal cord—I. Co-existence of galanin with other peptides in primary afferents in normal rats. Neuroscience 57, 365–384.PubMedCrossRefGoogle Scholar
  210. Zhang X., Nicholas A. P., and Hökfelt T. (1995b) Ultrastructural studies on peptides in the dorsal horn of the rat spinal cord—II. Co-existence of galanin with other peptides in local neurons. Neuroscience 64, 875–891.PubMedCrossRefGoogle Scholar
  211. Zini S., Roisin M. P., Armengaud C., and Ben-Ari Y. (1993a) Effect of potassium channel modulators on the release of glutamate induced by ischaemic-like conditions in rat hippocampal slices. Neurosci. Lett. 153, 202–205.PubMedCrossRefGoogle Scholar
  212. Zini S., Roisin M. P., Langel Ü., Bartfai T., and Ben-Ari Y. (1993b) Galanin reduces release of endogenous excitatory amino acids in the rat hippocampus. Eur. J. Pharmacol. 245, 1–7.PubMedCrossRefGoogle Scholar
  213. Ögren S. O., Kehr J., and Schott P. A. (1996) Effects of ventral hippocampal galanin on spatial learning and on in vivo acetylcholine release in the rat. Neuroscience 75, 1127–1140.PubMedCrossRefGoogle Scholar
  214. Ögren S. O., and Pramanik A. (1991) Galanin stimulates acetylcholine release in the rat striatum. Neurosci. Lett. 128, 253–256.PubMedCrossRefGoogle Scholar
  215. Ögren S. O., Schott P. A., Kehr J., et al. (1998) Modulation of acetylcholine and serotonin transmission by galanin. Relationship to spatial and aversive learning. Ann. NY. Acad. Sci. 863, 342–363.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Linda Lundström
    • 1
  • Anna Elmquist
    • 1
  • Tamas Bartfai
    • 2
  • Ülo Langel
    • 1
  1. 1.Department of Neurochemistry and NeurotoxicologyStockholm UniversityStockholmSweden
  2. 2.Department of NeuropharmacologyThe Scripps Research InstituteLa JollaUSA

Personalised recommendations