Skip to main content

Advertisement

Log in

Neurotrophic Factors in Autonomic Nervous System Plasticity and Dysfunction

  • Review Paper
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

During development, neurotrophic factors are known to play important roles in regulating the survival of neurons in the autonomic nervous system (ANS) and the formation of their synaptic connectivity with their peripheral targets in the cardiovascular, digestive, and other organ systems. Emerging findings suggest that neurotrophic factors may also affect the functionality of the ANS during adult life and may, in part, mediate the effects of environmental factors such as exercise and dietary energy intake on ANS neurons and target cells. In this article, we describe the evidence that ANS neurons express receptors for multiple neurotrophic factors, and data suggesting that activation of those receptors can modify plasticity in the ANS. Neurotrophic factors that may regulate ANS function include brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factors, and ciliary neurotrophic factor. The possibility that perturbed neurotrophic factor signaling is involved in the pathogenesis of ANS dysfunction in some neurological disorders is considered, together with implications for neurotrophic factor-based therapeutic interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aharon-Peretz, J., Harel, T., Revach, M., & Ben-Haim, S. A. (1992). Increased sympathetic and decreased parasympathetic cardiac innervation in patients with Alzheimer’s disease. Archives of Neurology, 49, 919–922

    PubMed  CAS  Google Scholar 

  • Ahmet, I., Wan, R., Mattson, M. P., Lakatta, E. G., & Talan, M. (2005). Cardioprotection by intermittent fasting in rats. Circulation, 112, 3115–3121.

    PubMed  Google Scholar 

  • Airaksinen, M. S., Holm, L., & Hatinen, T. (2006). Evolution of the GDNF family ligands and receptors. Brain Behavior and Evolution, 68, 181–190.

    Google Scholar 

  • Algotsson, A., Viitanen, M., Winblad, B., & Solders, G. (1995). Autonomic dysfunction in Alzheimer’s disease. Acta Neurologica Scandinavica, 91, 14–18.

    PubMed  CAS  Google Scholar 

  • Allan, L. M., Ballard, C. G., Allen, J., Murray, A., Davidson, A. W., McKeith, I. G., & Kenny, R. A. (2007). Autonomic dysfunction in dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 671–677.

    PubMed  CAS  Google Scholar 

  • Andrich, J., Schmitz, T., Saft, C., Postert, T., Kraus, P., Epplen, J. T., Przuntek, H., & Agelink, M. W. (2002). Autonomic nervous system function in Huntington’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 72, 726–731.

    PubMed  CAS  Google Scholar 

  • Anitha, M., Gondha, C., Sutliff, R., Parsadanian, A., Mwangi, S., Sitaraman, S. V., & Srinivasan, S. (2006). GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway. Journal of Clinical Investigation, 116, 344–356.

    PubMed  CAS  Google Scholar 

  • Arsenijevic, Y., & Weiss, S. (1998). Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: Distinct actions from those of brain-derived neurotrophic factor. Journal of Neuroscience, 18, 2118–2128.

    PubMed  CAS  Google Scholar 

  • Asai, N., Fukuda, T., Wu, Z., Enomoto, A., Pachnis, V., Takahashi, M., & Costantini, F. (2006). Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells. Development, 133, 4507–4516.

    PubMed  CAS  Google Scholar 

  • Awerbuch, G. I., & Sandyk, R. (1994). Autonomic functions in the early stages of Parkinson’s disease. The International Journal of Neuroscience, 74, 9–16.

    PubMed  CAS  Google Scholar 

  • Baloh, R. H., Enomoto, H., Johnson, E. M., Jr., & Milbrandt, J. (2000). The GDNF family ligands and receptors—implications for neural development. Current Opinions in Neurobiology, 10, 103–110.

    CAS  Google Scholar 

  • Barbacid, M. (1995). Structural and functional properties of the TRK family of neurotrophin receptors. Annals of the New York Academy of Sciences, 766, 442–458.

    PubMed  CAS  Google Scholar 

  • Bariohay, B., Lebrun, B., Moyse, E., & Jean, A. (2005). Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex. Endocrinology, 146, 5612–5620.

    PubMed  CAS  Google Scholar 

  • Berretta, S. (2005). Cortico-amygdala circuits: Role in the conditioned stress response. Stress, 8, 221–232.

    Article  PubMed  Google Scholar 

  • Bharmal, S., Slonimsky, J. D., Mead, J. N., Sampson, C. P., Tolkovsky, A. M., Yang, B., Bargman, R., & Birren, S. J. (2001). Target cells promote the development and functional maturation of neurons derived from a sympathetic precursor cell line. Developmental Neuroscience, 23, 153–164.

    PubMed  CAS  Google Scholar 

  • Birkhofer, A., Schmidt, G., & Forstl, H. (2005). Heart and brain—the influence of psychiatric disorders and their therapy on the heart rate variability. Fortschritte der Neurologie-Psychiatrie, 73, 192–205.

    PubMed  CAS  Google Scholar 

  • Boesmans, W., Gomes, P., Janssens, J., Tack, J., & Vanden Berghe, P. (2007). Brain-derived neurotrophic factor amplifies neurotransmitter responses and promotes synaptic communication in the enteric nervous system. Gut (Epub ahead of print).

  • Braak, H., Del Tredici, K., Rub, U., de Vos, R. A., Jansen Steur, E. N., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24, 197–211.

    PubMed  Google Scholar 

  • Braak, H., Sastre, M., Bohl, J. R., de Vos, R. A., & Del Tredici, K. (2007). Parkinson’s disease: Lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons. Acta Neuropathologica (Berl), 113, 421–429.

    Google Scholar 

  • Buj-Bello, A., Buchman, V. L., Horton, A., Rosenthal, A., & Davies, A. M. (1995). GDNF is an age-specific survival factor for sensory and autonomic neurons. Neuron, 15, 821–828.

    PubMed  CAS  Google Scholar 

  • Causing, C. G., Gloster, A., Aloyz, R., Bamji, S. X., Chang, E., Fawcett, J., Kuchel, G., & Miller, F. D. (1997). Synaptic innervation density is regulated by neuron-derived BDNF. Neuron, 18, 257–267.

    PubMed  CAS  Google Scholar 

  • Casscells, W., Speir, E., Sasse, J., Klagsbrun, M., Allen, P., Lee, M., Calvo, B., Chiba, M., Haggroth, L., & Folkman, J. (1990). Isolation, characterization, and localization of heparin-binding growth factors in the heart. Journal of Clinical Investigation, 85, 433–441.

    PubMed  CAS  Google Scholar 

  • Chalazonitis, A. (2004). Neurotrophin-3 in the development of the enteric nervous system. Progress in Brain Research, 146, 243–263.

    PubMed  CAS  Google Scholar 

  • Cheng, B., & Mattson, M. P. (1991). NGF and bFGF protect rat hippocampal and human cortical neurons against hypoglycemic damage by stabilizing calcium homeostasis. Neuron, 7, 1031–1041.

    PubMed  CAS  Google Scholar 

  • Cheng, B., McMahon, D. G., & Mattson, M. P. (1993). Modulation of calcium current, intracellular calcium levels and cell survival by glucose deprivation and growth factors in hippocampal neurons. Brain Research, 607, 275–285.

    PubMed  CAS  Google Scholar 

  • Chun, L. L., & Patterson, P. H. (1977). Role of nerve growth factor in the development of rat sympathetic neurons in vitro. I. Survival, growth, and differentiation of catecholamine production. The Journal of Cell Biology, 75, 694–704.

    PubMed  CAS  Google Scholar 

  • Claes, S. J. (2004). Corticotropin-releasing hormone (CRH) in psychiatry: From stress to psychopathology. Annals of Medicine, 36, 50–61.

    PubMed  CAS  Google Scholar 

  • Collins, F., & Dawson, A. (1983). An effect of nerve growth factor on parasympathetic neurite outgrowth. Proceedings of the National Academy of Sciences of the United States of America, 80, 2091–2094.

    PubMed  CAS  Google Scholar 

  • Connor, B., Young, D., Yan, Q., Faull, R. L., Synek, B., & Dragunow, M. (1997). Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Molecular Brain Research, 49, 71–81.

    PubMed  CAS  Google Scholar 

  • Cotman, C. W., Berchtold, N. C., & Christie, L. A. (2007). Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends in Neuroscience, 30, 464–472.

    CAS  Google Scholar 

  • Craddock, N., & Forty, L. (2006). Genetics of affective (mood) disorders. European Journal of Human Genetics, 14, 660–668.

    PubMed  CAS  Google Scholar 

  • Crouch, M. F., & Hendry, I. A. (1991). Co-activation of insulin-like growth factor-I receptors and protein kinase C results in parasympathetic neuronal survival. Journal of Neuroscience Research, 28, 115–120.

    PubMed  CAS  Google Scholar 

  • Crowell, M. D., & Wessinger, S. B. (2007). 5-HT and the brain-gut axis: Opportunities for pharmacologic intervention. Expert Opinion on Investigational Drugs, 16, 761–765.

    PubMed  CAS  Google Scholar 

  • DeRijk, R., & de Kloet, E. R. (2005). Corticosteroid receptor genetic polymorphisms and stress responsivity. Endocrine, 28, 263–270.

    PubMed  CAS  Google Scholar 

  • De Rosa, R., Garcia, A. A., Braschi, C., Capsoni, S., Maffei, L., Berardi, N., & Cattaneo, A. (2005). Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 102, 3811–3816.

    PubMed  Google Scholar 

  • Devos, D., Kroumova, M., Bordet, R., Vodougnon, H., Guieu, J. D., Libersa, C., & Destee, A. (2003). Heart rate variability and Parkinson’s disease severity. Journal of Neural Transmission, 110, 997–1011.

    PubMed  CAS  Google Scholar 

  • Dewey, R. B., Jr. (2004). Autonomic dysfunction in Parkinson’s disease. Neurologic Clinics, 22, S127–139.

    PubMed  Google Scholar 

  • DiCicco-Bloom, E., & Black, I. B. (1988). Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts. Proceedings of the National Academy of Sciences of the United States of America, 85, 4066–4070.

    PubMed  CAS  Google Scholar 

  • Distasi, C., Torre, M., Antoniotti, S., Munaron, L., & Lovisolo, D. (1998). Neuronal survival and calcium influx induced by basic fibroblast growth factor in chick ciliary ganglion neurons. European Journal of Neuroscience, 10, 2276–2286.

    PubMed  CAS  Google Scholar 

  • Doering, L. C., Roder, J. C., & Henderson, J. T. (1995). Ciliary neurotrophic factor promotes the terminal differentiation of v-myc immortalized sympathoadrenal progenitor cells in vivo. Developmental Brain Research, 89, 56–66.

    PubMed  CAS  Google Scholar 

  • Dono, R., Texido, G., Dussel, R., Ehmke, H., & Zeller, R. (1998). Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. EMBO Journal, 17, 4213–4225.

    PubMed  CAS  Google Scholar 

  • Duan, W., Guo, Z., Jiang, H., Ware, M., & Mattson, M. P. (2003a). Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor. Endocrinology, 144, 2446–2453.

    PubMed  CAS  Google Scholar 

  • Duan, W., Guo, Z., Jiang, H., Ware, M., Li, X. J., & Mattson, M. P. (2003b). Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proceedings of the National Academy of Sciences of the United States of America, 100, 2911–2916.

    PubMed  CAS  Google Scholar 

  • Ebendal, T., Tomac, A., Hoffer, B. J., & Olson, L. (1995). Glial cell line-derived neurotrophic factor stimulates fiber formation and survival in cultured neurons from peripheral autonomic ganglia. Journal of Neuroscience Research, 40, 276–284.

    PubMed  CAS  Google Scholar 

  • Edgar, D., Barde, Y. A., & Thoenen, H. (1981). Subpopulations of cultured chick sympathetic neurones differ in their requirements for survival factors. Nature 289, 294–295.

    PubMed  CAS  Google Scholar 

  • Ekblad, E., & Bauer, A. J. (2004). Role of vasoactive intestinal peptide and inflammatory mediators in enteric neuronal plasticity. Neurogastroenterology and Motility, 16, S123–128.

    Google Scholar 

  • Enomoto, H., Araki, T., Jackman, A., Heuckeroth, R. O., Snider, W. D., Johnson, E. M., Jr., & Milbrandt, J. (1998). GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron, 21, 317–324.

    PubMed  CAS  Google Scholar 

  • Eswarakumar, V. P., Lax, I., & Schlessinger, J. (2005). Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Reviews, 16, 139–149.

    PubMed  CAS  Google Scholar 

  • Ferrer, I., Goutan, E., Marin, C., Rey, M. J., & Ribalta, T. (2000). Brain-derived neurotrophic factor in Huntington disease. Brain Research, 866, 257–261.

    PubMed  CAS  Google Scholar 

  • Ferrer, I., Marin, C., Rey, M. J., Ribalta, T., Goutan, E., Blanco, R., Tolosa, E., & Marti, E. (1999). BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. Journal of Neuropathology and Experimental Neurology, 58, 729–739.

    PubMed  CAS  Google Scholar 

  • Francke, U. (2006). Mechanisms of disease: Neurogenetics of MeCP2 deficiency. Nature Clinical Practice Neurology, 2, 212–221.

    PubMed  CAS  Google Scholar 

  • Ginsberg, S. D., Che, S., Wuu, J., Counts, S. E., & Mufson, E. J. (2006). Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer’s disease. Journal of Neurochemistry, 97, 475–487.

    PubMed  CAS  Google Scholar 

  • Giubilei, F., Strano, S., Imbimbo, B. P., Tisei, P., Calcagnini, G., Lino, S., Frontoni, M., Santini, M., & Fieschi, C. (1998). Cardiac autonomic dysfunction in patients with Alzheimer disease: Possible pathogenetic mechanisms. Alzheimer Disease and Associated Disorders, 12, 356–361.

    Article  PubMed  CAS  Google Scholar 

  • Gorman, J. M., & Sloan, R. P. (2000). Heart rate variability in depressive and anxiety disorders. American Heart Journal, 40, 77–83.

    Google Scholar 

  • Halagappa, V. K., Guo, Z., Pearson, M., Matsuoka, Y., Cutler, R. G., Laferla, F. M., & Mattson, M. P. (2007). Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiology of Disease, 26, 212–220.

    PubMed  CAS  Google Scholar 

  • Hasan, W., & Smith, P. G. (2000). Nerve growth factor expression in parasympathetic neurons: Regulation by sympathetic innervation. European Journal of Neuroscience, 12, 4391–4397.

    PubMed  CAS  Google Scholar 

  • Hazari, M. S., Pan, J. H., & Myers, A. C. (2007). Nerve growth factor acutely potentiates synaptic transmission in vitro and induces dendritic growth in vivo on adult neurons in airway parasympathetic ganglia. American Journal of Physiology. Lung Cellular and Molecular Physiology, 292, L992–1001.

    PubMed  CAS  Google Scholar 

  • Helke, C. J., Adryan, K. M., Fedorowicz, J., Zhuo, H., Park, J. S., Curtis, R., Radley, H. E., & Distefano, P. S. (1998). Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat. The Journal of Comparitive Neurology, 393, 102–117.

    CAS  Google Scholar 

  • Hock, C., Heese, K., Muller-Spahn, F., Hulette, C., Rosenberg, C., & Otten, U. (1998). Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer’s disease. Neuroscience Letters, 241, 151–154.

    PubMed  CAS  Google Scholar 

  • Hottenrott, K., Hoos, O., & Esperer, H. D. (2006). Heart rate variability and physical exercise. Current status. Herz, 31, 544–552.

    PubMed  Google Scholar 

  • Hou, R. H., Samuels, E. R., Raisi, M., Langley, R. W., Szabadi, E., & Bradshaw, C. M. (2006). Why patients with Alzheimer’s disease may show increased sensitivity to tropicamide eye drops: Role of locus coeruleus. Psychopharmacology (Berl), 184, 95–106.

    CAS  Google Scholar 

  • Hurelbrink, C. B., & Barker, R. A. (2001). Prospects for the treatment of Parkinson’s disease using neurotrophic factors. Expert Opinion on Pharmacotherapy, 2, 1531–1543.

    PubMed  CAS  Google Scholar 

  • Ip, N. Y., Boulton, T. G., Li, Y., Verdi, J. M., Birren, S. J., Anderson, D. J., & Yancopoulos, G. D. (1994). NTF, FGF, and NGF collaborate to drive the terminal differentiation of MAH cells into postmitotic neurons. Neuron, 13, 443–455.

    PubMed  CAS  Google Scholar 

  • Johnson, J. B., Summer, W., Cutler, R. G., Martin, B., Hyun, D. H., Dixit, V. D., Pearson, M., Nassar, M., Tellejohan, R., Maudsley, S., Carlson, O., John, S., Laub, D. R., & Mattson, M. P. (2007). Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radical Biology & Medicine, 42, 665–674.

    CAS  Google Scholar 

  • Jordan, D. (2005). Vagal control of the heart: Central serotonergic (5-HT). mechanisms. Experimental Physiology, 90, 175–181.

    PubMed  CAS  Google Scholar 

  • Kallio, M., Haapaniemi, T., Turkka, J., Suominen, K., Tolonen, U., Sotaniemi, K., Heikkila, V. P., & Myllyla, V. (2000). Heart rate variability in patients with untreated Parkinson’s disease. European Journal of Neurology, 7, 667–672.

    PubMed  CAS  Google Scholar 

  • Karagiannis, S. N., King, R. H., & Thomas, P. K. (1997). Colocalisation of insulin and IGF-1 receptors in cultured rat sensory and sympathetic ganglion cells. Journal of Anatomy, 191, 431–440.

    PubMed  CAS  Google Scholar 

  • Kasselman, L. J., Sideris, A., Bruno, C., Perez, W. R., Cai, N., Nicoletti, J. N., Wiegand, S. J., & Croll, S. D. (2006). BDNF: A missing link between sympathetic dysfunction and inflammatory disease? Journal of Neuroimmunology, 175, 118–127.

    PubMed  CAS  Google Scholar 

  • Kelly-Spratt, K. S., Klesse, L. J., & Parada, L. F. (2002). BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons through Ras and PI-3 kinase signaling. Journal of Neuroscience Research, 69, 151–159.

    PubMed  CAS  Google Scholar 

  • Kessler, J. A., & Black, I. B. (1980). The effects of nerve growth factor (NGF). and antiserum to NGF on the development of embryonic sympathetic neurons in vivo. Brain Research, 189, 157–168.

    PubMed  CAS  Google Scholar 

  • Klimaschewski, L., Meisinger, C., & Grothe, C. (1999). Localization and regulation of basic fibroblast growth factor (FGF-2) and FGF receptor-1 in rat superior cervical ganglion after axotomy. Journal of Neurobiology, 38, 499–506.

    PubMed  CAS  Google Scholar 

  • Kobal, J., Meglic, B., Mesec, A., & Peterlin, B. (2004). Early sympathetic hyperactivity in Huntington’s disease. European Journal of Neurology, 11, 842–848.

    PubMed  CAS  Google Scholar 

  • Kwon, B. K., Liu, J., Lam, C., Plunet, W., Oschipok, L. W., Hauswirth, W., Di Polo, A., Blesch, A., & Tetzlaff, W. (2007). Brain-derived neurotrophic factor gene transfer with adeno-associated viral and lentiviral vectors prevents rubrospinal neuronal atrophy and stimulates regeneration-associated gene expression after acute cervical spinal cord injury. Spine, 32, 1164–1173.

    PubMed  Google Scholar 

  • Kyrou, I., & Tsigos, C. (2007). Stress mechanisms and metabolic complications. Hormone and Metabolic Research, 39, 430–438.

    PubMed  CAS  Google Scholar 

  • Laustsen, P. G., Russell, S. J., Cui, L., Entingh-Pearsall, A., Holzenberger, M., Liao, R., & Kahn, C. R. (2007). Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Molecular Cell Biology, 27, 1649–1664.

    CAS  Google Scholar 

  • Lechin, F., van der Dijs, B., Orozco, B., Lechin, A. E., Baez, S., Lechin, M. E., Rada, I., Acosta, E., Arocha, L., Jimenez, V., et al. (1995). Plasma neurotransmitters, blood pressure, and heart rate during supine resting, orthostasis, and moderate exercise in dysthymic depressed patients. Biological Psychiatry, 37, 884–891.

    PubMed  CAS  Google Scholar 

  • Lee, J., Duan, W., & Mattson, M. P. (2002b). Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. Journal of Neurochemistry, 82, 1367–1375.

    PubMed  CAS  Google Scholar 

  • Lee, P. G., Hohman, T. C., Cai, F., Regalia, J., & Helke, C. J. (2001). Streptozotocin-induced diabetes causes metabolic changes and alterations in neurotrophin content and retrograde transport in the cervical vagus nerve. Experimental Neurology, 170, 149–161.

    PubMed  CAS  Google Scholar 

  • Lee, J., Seroogy, K. B., & Mattson, M. P. (2002a). Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. Journal of Neurochemistry, 80, 539–547.

    PubMed  CAS  Google Scholar 

  • LeVatte, M. A., Dekaban, G. A., & Weaver, L. C. (1997). Gene transfer into sympathetic preganglionic neurons in vivo using a non-replicating thymidine kinase-deficient herpes simplex virus type 1. Neuroscience, 80, 893–906.

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini, R., & Calissano, P. (1979). The nerve-growth factor. Scientific American, 240, 44–53.

    Article  Google Scholar 

  • Levivier, M., Przedborski, S., Bencsics, C., & Kang, U. J. (1995). Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease. Journal of Neuroscience, 15, 7810–7820.

    PubMed  CAS  Google Scholar 

  • Lockhart, S. T., Mead, J. N., Pisano, J. M., Slonimsky, J. D., & Birren, S. J. (2000). Nerve growth factor collaborates with myocyte-derived factors to promote development of presynaptic sites in cultured sympathetic neurons. Journal of Neurobiology, 42, 460–476.

    PubMed  CAS  Google Scholar 

  • Lockhart, S. T., Turrigiano, G. G., & Birren, S. J. (1997). Nerve growth factor modulates synaptic transmission between sympathetic neurons and cardiac myocytes. Journal of Neuroscience, 17, 9573–9582.

    PubMed  CAS  Google Scholar 

  • Loewenthal, N., Levy, J., Schreiber, R., Pinsk, V., Perry, Z., Shorer, Z., & Hershkovitz, E. (2005). Nerve growth factor-tyrosine kinase A pathway is involved in thermoregulation and adaptation to stress: Studies on patients with hereditary sensory and autonomic neuropathy type IV. Pediatric Research, 57, 587–590.

    PubMed  CAS  Google Scholar 

  • Lynch, G., Kramar, E. A., Rex, C. S., Jia, Y., Chappas, D., Gall, C. M., & Simmons, D. A. (2007). Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington’s disease. Journal of Neuroscience, 27, 4424–4434.

    PubMed  CAS  Google Scholar 

  • Mager, D. E., Wan, R., Brown, M., Cheng, A., Wareski, P., Abernethy, D. R., & Mattson, M. P. (2006). Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB Journal, 20, 631–637.

    PubMed  CAS  Google Scholar 

  • Malaspina, D., Dalack, G., Leitman, D., Corcoran, C., Amador, X. F., Yale, S., Glassman, A., & Gorman, J. M. (2002). Low heart rate variability is not caused by typical neuroleptics in schizophrenia patients. CNS Spectrums, 7, 53–57.

    PubMed  Google Scholar 

  • Martinelli, P. M., Camargos, E. R., Azevedo, A. A., Chiari, E., Morel, G., & Machado, C. R. (2006). Cardiac NGF and GDNF expression during Trypanosoma cruzi infection in rats. Autonomic Neuroscience, 130, 32–40.

    PubMed  CAS  Google Scholar 

  • Martini, G., Riva, P., Rabbia, F., Molini, V., Ferrero, G. B., Cerutti, F., Carra, R., & Veglio, F. (2001). Heart rate variability in childhood obesity. Clinical Autonomic Research, 11, 87–91.

    PubMed  CAS  Google Scholar 

  • Martinowich, K., & Lu, B. (2007). Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology, 33, 73–83.

    Google Scholar 

  • Mastrocola, C., Vanacore, N., Giovani, A., Locuratolo, N., Vella, C., Alessandri, A., Baratta, L., Tubani, L., & Meco, G. (1999). Twenty-four-hour heart rate variability to assess autonomic function in Parkinson’s disease. Acta Neurologica Scandinavica, 99, 245–247.

    PubMed  CAS  Google Scholar 

  • Maswood, N., Young, J., Tilmont, E., Zhang, Z., Gash, D. M., Gerhardt, G. A., Grondin, R., Roth, G. S., Mattison, J., Lane, M. A., Carson, R. E., Cohen, R. M., Mouton, P. R., Quigley, C., Mattson, M. P., & Ingram, D. K. (2004). Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America, 101, 18171–18176.

    PubMed  CAS  Google Scholar 

  • Matsuoka, Y., Gray, A. J., Hirata-Fukae, C., Minami, S. S., Waterhouse, E. G., Mattson, M. P., LaFerla, F. M., Gozes, I., & Aisen, P. S. (2007). Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer’s disease at early pathological stage. Journal of Molecular Neuroscience, 31, 165–170.

    PubMed  CAS  Google Scholar 

  • Mattson, M. P., & Cheng, A. (2006). Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses. Trends in Neuroscience, 29, 632–639.

    CAS  Google Scholar 

  • Mattson, M. P., Maudsley, S., & Martin, B. (2004). A neural signaling triumvirate that influences ageing and age-related disease: Insulin/IGF-1, BDNF and serotonin. Ageing Research Reviews, 3, 445–464.

    PubMed  CAS  Google Scholar 

  • Mattson, M. P., Murrain, M., Guthrie, P. B., & Kater, S. B. (1989). Fibroblast growth factor and glutamate: Opposing roles in the generation and degeneration of hippocampal neuroarchitecture. Journal of Neuroscience, 9, 3728–3740.

    PubMed  CAS  Google Scholar 

  • Mattson, M. P., & Wan, R. (2005). Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. The Journal of Nutritional Biochemistry, 16, 129–137.

    PubMed  CAS  Google Scholar 

  • Mattson, M. P., Zhang, Y., & Bose, S. (1993). Growth factors prevent mitochondrial dysfunction, loss of calcium homeostasis, and cell injury, but not ATP depletion in hippocampal neurons deprived of glucose. Experimental Neurology, 121, 1–13.

    PubMed  CAS  Google Scholar 

  • Mijatovic, J., Airavaara, M., Planken, A., Auvinen, P., Raasmaja, A., Piepponen, T. P., Costantini, F., Ahtee, L., & Saarma, M. (2007). Constitutive Ret activity in knock-in multiple endocrine neoplasia type B mice induces profound elevation of brain dopamine concentration via enhanced synthesis and increases the number of TH-positive cells in the substantia nigra. Journal of Neurosciences, 27, 4799–4809.

    CAS  Google Scholar 

  • Mogi, M., Togari, A., Kondo, T., Mizuno, Y., Komure, O., Kuno, S., Ichinose, H., & Nagatsu, T. (1999). Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Letters, 270, 45–48.

    CAS  Google Scholar 

  • Mohan, R. M., Golding, S., Heaton, D. A., Danson, E. J., & Paterson, D. J. (2004). Targeting neuronal nitric oxide synthase with gene transfer to modulate cardiac autonomic function. Progress in Biophysics and Molecular Biology, 84, 321–344.

    PubMed  CAS  Google Scholar 

  • Mufson, E. J., Lavine, N., Jaffar, S., Kordower, J. H., Quirion, R., & Saragovi, H. U. (1997). Reduction in p140-TrkA receptor protein within the nucleus basalis and cortex in Alzheimer’s disease. Experimental Neurology, 146, 91–103.

    PubMed  CAS  Google Scholar 

  • Nakagawa, T., Ono-Kishino, M., Sugaru, E., Yamanaka, M., Taiji, M., & Noguchi, H. (2002). Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice. Diabetes Metabolism Research Reviews., 18, 185–191.

    CAS  Google Scholar 

  • Neeper, S. A., Gomez-Pinilla, F., Choi, J., & Cotman, C. W. (1996). Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Research, 726, 49–56.

    PubMed  CAS  Google Scholar 

  • Nelson, R. L., Guo, Z., Halagappa, V. M., Pearson, M., Gray, A. J., Matsuoka, Y., Brown, M., Martin, B., Iyun, T., Maudsley, S., Clark, R. F., & Mattson, M. P. (2007). Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3×TgAD mice. Experimental Neurology, 205, 166–176.

    PubMed  CAS  Google Scholar 

  • Nomura, Y., Kimura, K., Arai, H., & Segawa, M. (1997). Involvement of the autonomic nervous system in the pathophysiology of Rett syndrome. European Child Adolescent Psychiatry, 6, S42–46.

    Google Scholar 

  • Oka, H., Mochio, S., Onouchi, K., Morita, M., Yoshioka, M., & Inoue, K. (2006). Cardiovascular dysautonomia in de novo Parkinson’s disease. Journal of Neurological Sciences, 241, 59–65.

    Google Scholar 

  • Parain, K., Murer, M. G., Yan, Q., Faucheux, B., Agid, Y., Hirsch, E., & Raisman-Vozari, R. (1999). Reduced expression of brain-derived neurotrophic factor protein in Parkinson’s disease substantia nigra. Neuroreport, 10, 557–561.

    PubMed  CAS  Google Scholar 

  • Paterson, D. S., Thompson, E. G., Belliveau, R. A., Antalffy, B. A., Trachtenberg, F. L., Armstrong, D. D., & Kinney, H. C. (2005). Serotonin transporter abnormality in the dorsal motor nucleus of the vagus in Rett syndrome: potential implications for clinical autonomic dysfunction. Journal of Neuropathology and Experimental Neurology, 64, 1018–1027.

    PubMed  CAS  Google Scholar 

  • Peiris, T. S., Machaalani, R., & Waters, K. A. (2004). Brain-derived neurotrophic factor mRNA and protein in the piglet brainstem and effects of intermittent hypercapnic hypoxia. Brain Research, 1029, 11–23.

    PubMed  CAS  Google Scholar 

  • Phillips, H. S., Hains, J. M., Armanini, M., Laramee, G. R., Johnson, S. A., & Winslow, J. W. (1991). BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron, 7, 695–702.

    PubMed  CAS  Google Scholar 

  • Puri, P., & Shinkai, T. (2004). Pathogenesis of Hirschsprung’s disease and its variants: Recent progress. Seminars in Pediatric Surgery, 13, 18–24.

    PubMed  Google Scholar 

  • Pursiainen, V., Korpelainen, J. T., Huikuri, H. V., Sotaniemi, K. A., & Myllyla, V. V. (2002). Circadian heart rate variability in Parkinson’s disease. Journal of Neurology, 249, 1535–1540.

    PubMed  Google Scholar 

  • Reichardt, L. F. (2006). Neurotrophin-regulated signalling pathways. Philosophical Transactions of the Royal Society of London Series B Biological Sciences, 361, 1545–1564.

    CAS  Google Scholar 

  • Reimer, M. K., Mokshagundam, S. P., Wyler, K., Sundler, F., Ahren, B., & Stagner, J. I. (2003). Local growth factors are beneficial for the autonomic reinnervation of transplanted islets in rats. Pancreas, 26, 392–397.

    PubMed  CAS  Google Scholar 

  • Reiss, K., Kajstura, J., Zhang, X., Li, P., Szoke, E., Olivetti, G., & Anversa, P. (1994). Acute myocardial infarction leads to upregulation of the IGF-1 autocrine system, DNA replication, and nuclear mitotic division in the remaining viable cardiac myocytes. Experimental Cell Research, 213, 463–472.

    PubMed  CAS  Google Scholar 

  • Roosen, A., Schober, A., Strelau, J., Bottner, M., Faulhaber, J., Bendner, G., McIlwrath, S. L., Seller, H., Ehmke, H., Lewin, G. R., & Unsicker, K. (2001). Lack of neurotrophin-4 causes selective structural and chemical deficits in sympathetic ganglia and their preganglionic innervation. Journal of Neuroscience, 21, 3073–3084.

    PubMed  CAS  Google Scholar 

  • Rosenwinkel, E. T., Bloomfield, D. M., Arwady, M. A., & Goldsmith, R. L. (2001). Exercise and autonomic function in health and cardiovascular disease. Cardiology Clinics, 19, 369–387.

    PubMed  CAS  Google Scholar 

  • Rossi, J., Herzig, K. H., Voikar, V., Hiltunen, P. H., Segerstrale, M., & Airaksinen, M. S. (2003). Alimentary tract innervation deficits and dysfunction in mice lacking GDNF family receptor alpha2. Journal of Clinical Investigation, 112, 707–716.

    PubMed  CAS  Google Scholar 

  • Sariola, H., & Saarma, M. (2003). Novel functions and signalling pathways for GDNF. Journal of Cell Science, 116, 3855–3862.

    PubMed  CAS  Google Scholar 

  • Sawada, H., Ibi, M., Kihara, T., Urushitani, M., Nakanishi, M., Akaike, A., & Shimohama, S. (2000). Neuroprotective mechanism of glial cell line-derived neurotrophic factor in mesencephalic neurons. Journal of Neurochemistry, 74, 1175–1184.

    PubMed  CAS  Google Scholar 

  • Schmidt, R. E., Dorsey, D. A., Beaudet, L. N., Parvin, C. A., & Escandon, E. (2001). Effect of NGF and neurotrophin-3 treatment on experimental diabetic autonomic neuropathy. Journal of Neuropathology and Experimantal Neurology, 60, 263–273.

    CAS  Google Scholar 

  • Schmidt, R. E., Dorsey, D. A., Beaudet, L. N., Plurad, S. B., Parvin, C. A., & Miller, M. S. (1999). Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy. American Journal of Pathology, 155, 1651–1660.

    PubMed  CAS  Google Scholar 

  • Schober, A., Minichiello, L., Keller, M., Huber, K., Layer, P. G., Roig-Lopez, J. L., Garcia-Arraras, J. E., Klein, R., & Unsicker, K. (1997). Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice. Journal of Neuroscience, 17, 891–903.

    PubMed  CAS  Google Scholar 

  • Schober, A., Wolf, N., Huber, K., Hertel, R., Krieglstein, K., Minichiello, L., Kahane, N., Widenfalk, J., Kalcheim, C., Olson, L., Klein, R., Lewin, G. R., & Unsicker, K. (1998). TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla. Journal of Neuroscience, 18, 7272–7284.

    PubMed  CAS  Google Scholar 

  • Silani, V., Borasio, G. D., Zhou, F. C., Bernasconi, S., Pizzuti, A., Sampietro, A., & Scarlato, G. (1994). NGF-response of EGF-dependent progenitor cells obtained from human sympathetic ganglia. Neuroreport, 5, 2085–2089.

    PubMed  CAS  Google Scholar 

  • Sleeman, M. W., Anderson, K. D., Lambert, P. D., Yancopoulos, G. D., & Wiegand, S. J. (2000). The ciliary neurotrophic factor and its receptor, CNTFR alpha. Pharmaceutica Acta Helvetiae, 74, 265–272.

    PubMed  CAS  Google Scholar 

  • Slevin, J. T., Gash, D. M., Smith, C. D., Gerhardt, G. A., Kryscio, R., Chebrolu, H., Walton, A., Wagner, R., & Young, A. B. (2007). Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal. Journal of Neurosurgery, 106, 614–620.

    PubMed  CAS  Google Scholar 

  • Slonimsky, J. D., Yang, B., Hinterneder, J. M., Nokes, E. B., & Birren, S. J. (2003). BDNF and CNTF regulate cholinergic properties of sympathetic neurons through independent mechanisms. Molecular and Cellular Neuroscience, 23, 648–660.

    PubMed  CAS  Google Scholar 

  • Speir, E., Tanner, V., Gonzalez, A. M., Farris, J., Baird, A., & Casscells, W. (1992). Acidic and basic fibroblast growth factors in adult rat heart myocytes. Localization, regulation in culture, and effects on DNA synthesis. Circulation Research, 71, 251–259.

    PubMed  CAS  Google Scholar 

  • Spires, T. L., Grote, H. E., Varshney, N. K., Cordery, P. M., van Dellen, A., Blakemore, C., & Hannan, A. J. (2004). Environmental enrichment rescues protein deficits in a mouse model of Huntington’s disease, indicating a possible disease mechanism. Journal of Neuroscience, 24, 2270–2276.

    PubMed  CAS  Google Scholar 

  • Taraviras, S., Marcos-Gutierrez, C. V., Durbec, P., Jani, H., Grigoriou, M., Sukumaran, M., Wang, L. C., Hynes, M., Raisman, G., & Pachnis, V. (1999). Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. Development, 126, 2785–2797.

    PubMed  CAS  Google Scholar 

  • Thrasivoulou, C., Soubeyre, V., Ridha, H., Giuliani, D., Giaroni, C., Michael, G. J., Saffrey, M. J., & Cowen, T. (2006). Reactive oxygen species, dietary restriction and neurotrophic factors in age-related loss of myenteric neurons. Aging Cell, 5, 247–257.

    PubMed  CAS  Google Scholar 

  • Tucker, P., Beebe, K. L., Burgin, C., Wyatt, D. B., Parker, D. E., Masters, B. K., & Nawar, O. (2004). Paroxetine treatment of depression with posttraumatic stress disorder: Effects on autonomic reactivity and cortisol secretion. Journal of Clinical Psychopharmacology, 24, 131–140.

    PubMed  CAS  Google Scholar 

  • Tyler, C. M., & Federoff, H. J. (2006). CNS gene therapy and a nexus of complexity: Systems and biology at a crossroads. Cell Transplantation, 15, 267–273.

    PubMed  Google Scholar 

  • Vinik, A. I., Maser, R. E., Mitchell, B. D., & Freeman, R. (2003). Diabetic autonomic neuropathy. Diabetes Care, 26, 1553–1579.

    PubMed  Google Scholar 

  • von Boyen, G. B., Reinshagen, M., Steinkamp, M., Adler, G., & Kirsch, J. (2002). Enteric nervous plasticity and development: Dependence on neurotrophic factors. Journal of Gastroenterology, 37, 583–588.

    Google Scholar 

  • Wakabayashi, K., & Takahashi, H. (1997). Neuropathology of autonomic nervous system in Parkinson’s disease. European Neurology, 38, S2–7.

    Google Scholar 

  • Wan, R., Camandola, S., & Mattson, M. P. (2003a). Intermittent food deprivation improves cardiovascular and neuroendocrine responses to stress in rats. Journal of Nutrition, 133, 1921–1929.

    PubMed  CAS  Google Scholar 

  • Wan, R., Camandola, S., & Mattson, M. P. (2003b). Intermittent fasting and dietary supplementation with 2-deoxy-d-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB Journal, 17, 1133–1134.

    PubMed  CAS  Google Scholar 

  • Wang, X., & Halvorsen, S. W. (1998). Reciprocal regulation of ciliary neurotrophic factor receptors and acetylcholine receptors during synaptogenesis in embryonic chick atria. Journal of Neuroscience, 18, 7372–7380.

    PubMed  CAS  Google Scholar 

  • Wang, H., & Zhou, X. F. (2002). Injection of brain-derived neurotrophic factor in the rostral ventrolateral medulla increases arterial blood pressure in anaesthetized rats. Neuroscience, 112, 967–975.

    PubMed  CAS  Google Scholar 

  • Williams, B. J., Eriksdotter-Jonhagen, M., & Granholm, A. C. (2006). Nerve growth factor in treatment and pathogenesis of Alzheimer’s disease. Progress in Neurobiology, 80, 114–128.

    PubMed  CAS  Google Scholar 

  • Wolf, S. A., Kronenberg, G., Lehmann, K., Blankenship, A., Overall, R., Staufenbiel, M., & Kempermann, G. (2006). Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer’s disease. Biological Psychiatry, 60, 1314–1323.

    PubMed  CAS  Google Scholar 

  • Wooten, M. W., Vandenplas, M. L., Seibenhener, M. L., Geetha, T., & Diaz-Meco, M. T. (2001). Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase C’s via a src kinase pathway. Molecular Cell Biology, 21, 8414–8427.

    CAS  Google Scholar 

  • Xu, B., Goulding, E. H., Zang, K., Cepoi, D., Cone, R. D., Jones, K. R., Tecott, L. H., & Reichardt, L. F. (2003). Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nature Neuroscience, 6, 736–742.

    PubMed  CAS  Google Scholar 

  • Yang, B., Slonimsky, J. D., & Birren, S. J. (2002). A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Nature Neuroscience, 5, 539–545.

    PubMed  CAS  Google Scholar 

  • York, R. D., Molliver, D. C., Grewal, S. S., Stenberg, P. E., McCleskey, E. W., & Stork, P. J. (2000). Role of phosphoinositide 3-kinase and endocytosis in nerve growth factor-induced extracellular signal-regulated kinase activation via Ras and Rap1. Molecular Cell Biology, 20, 8069–8083.

    CAS  Google Scholar 

  • Zaidi, S. I., Jafri, A., Doggett, T., & Haxhiu, M. A. (2005). Airway-related vagal preganglionic neurons express brain-derived neurotrophic factor and TrkB receptors: Implications for neuronal plasticity. Brain Research, 1044, 133–143.

    PubMed  CAS  Google Scholar 

  • Zahn, T. P. (1988). Studies of autonomic psychophysiology and attention in schizophrenia. Schizophrenia Bulletin, 14, 205–208.

    PubMed  CAS  Google Scholar 

  • Zhou, X., Nai, Q., Chen, M., Dittus, J. D., Howard, M. J., & Margiotta, J. F. (2004). Brain-derived neurotrophic factor and trkB signaling in parasympathetic neurons: relevance to regulating alpha7-containing nicotinic receptors and synaptic function. Journal of Neuroscience, 24, 4340–4350.

    PubMed  CAS  Google Scholar 

  • Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B. R., Goffredo, D., Conti, L., MacDonald, M. E., Friedlander, R. M., Silani, V., Hayden, M. R., Timmusk, T., Sipione, S., & Cattaneo, E. (2001). Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science, 293, 493–498.

    PubMed  CAS  Google Scholar 

  • Zulli, R., Nicosia, F., Borroni, B., Agosti, C., Prometti, P., Donati, P., De Vecchi, M., Romanelli, G., Grassi, V., & Padovani, A. (2005). QT dispersion and heart rate variability abnormalities in Alzheimer’s disease and in mild cognitive impairment. Journal of the American Geriatrics Society, 53, 2135–2139.

    PubMed  Google Scholar 

Download references

Acknowledgement

This research was supported by the Intramural Research Program of the National Institute on Aging, NIH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark P. Mattson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mattson, M.P., Wan, R. Neurotrophic Factors in Autonomic Nervous System Plasticity and Dysfunction. Neuromol Med 10, 157–168 (2008). https://doi.org/10.1007/s12017-007-8021-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-007-8021-y

Keywords

Navigation