Skip to main content
SpringerLink
Log in
Book cover

Molecular Neurosurgery With Targeted Toxins pp 31–58Cite as

Biochemical, Physiological, and Behavioral Characterizations of the Cholinergic Basal Forebrain Lesion Produced by 192 IgG-Saporin

  • Chapter

Abstract

Selective lesioning of the cholinergic neurons in the basal forebrain nuclei was a highly sought goal for use as an animal model of Alzheimer’s disease. Autopsy studies of Alzheimer’s-diseased brain tissue found that a substantial loss of the cholinergic innervation of the cerebral cortex and hippocampus was a prominent feature of this disease, and the degree of this neuron loss was highly correlated with the degree of dementia (1,2). Subsequent research confirmed that cholinergic neurons originating in the nucleus basalis of Meynert, the diagonal band of Broca, and the medial septal nucleus, which terminate mainly in the cortex, olfactory bulb, and hippocampus (3,4), are destroyed in the progression of Alzheimer’s disease. This loss occurred earlier than the degeneration of other types of neurons, and the scale of this cholinergic cell death was massive. The similarity to dopaminergic depletion in Parkinson’s disease was evident, and the cholinergic hypothesis for the dementia of Alzheimer’s disease was proposed. The need for an animal model to test therapeutic strategies fueled basic research about the function of this cholinergic basal forebrain (CBF) system.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 1981;10:122–126.

    Article  PubMed  CAS  Google Scholar 

  2. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978;25:1457–1459.

    Article  Google Scholar 

  3. Bigl V, Woolf NJ, Butcher LL. Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a com-bined fluorescent tracer and acetylcholinesterase analysis. Brain Res Bull 1982;8:727–749.

    Article  PubMed  CAS  Google Scholar 

  4. Mesulam M-M, Mufson EJ, Wainer BH, Levey AI. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature. Neuroscience 1983;10:1185–1201.

    Article  PubMed  CAS  Google Scholar 

  5. Dekker AJAM, Connor DJ, Thal LJ. The role of cholinergic projections from the nucleus basalis in memory. Neurosci Biobehav Rev 1991;15:299–317.

    Article  PubMed  CAS  Google Scholar 

  6. Choi DW. Excitotoxic cell death. J Neurobiol 1992;23:1261–1276.

    Article  PubMed  CAS  Google Scholar 

  7. Dunnett SB, Whishaw IQ, Jones GH, Bunch ST. Behavioural, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats. Neuroscience 1987;20:653–669.

    Article  PubMed  CAS  Google Scholar 

  8. Lindefors N, Boatell ML, Mahy N, Persson H. Widespread neuronal degeneration after ibotenic acid lesioning of cholinergic neurons in the nucleus basalis revealed by in situ hybridization. Neurosci Lett 1992;135:262–264.

    Article  PubMed  CAS  Google Scholar 

  9. Page KJ, Sirinathsinghji DJS, Everitt BJ. AMPA-induced lesions of the basal forebrain differentially affect cholinergic and non-cholinergic neurons: lesion assessment using quantitative in situ hybridization histochemistry. Eur J Neurosci 1995;7:1012–1021.

    Article  PubMed  CAS  Google Scholar 

  10. Gaal G, Potter PE, Hanin I, Kakucska I, Vizi ES. Effects of intracerebroventricular AF64A administration on cholinergic, serotoninergic and catecholaminergic circuitry in rat dorsal hippocampus. Neuroscience 1986;19:1197–1205.

    Article  PubMed  CAS  Google Scholar 

  11. Nakamura S, Tani Y, Maezono Y, Ishihara T, Ohno T. Learning deficits after unilateral AF64A lesions in the rat basal forebrain: role of cholinergic and noncholinergic systems. Pharmacol Biochem Behav 1992;42:119–130.

    Article  PubMed  CAS  Google Scholar 

  12. Meana JJ, Johansson B, Herrera-Marschitz M, et al. Effect of the neurotoxin AF64A on intrinsic and extrinsic neuronal systems of rat neostriatum measured by in vivo microdialysis. Brain Res 1992;596:65–72.

    Article  PubMed  CAS  Google Scholar 

  13. Wiley RG, Stirpe F, Thorpe P, Oeltmann TN. Neuronotoxic effects of monoclonal anti-Thy 1 antibody (OX7) coupled to the ribosome inactivating protein, saporin, as studied by suicide transport experiments in the rat. Brain Res 1989;505:44–54.

    Article  PubMed  CAS  Google Scholar 

  14. Contestabile A, Stirpe F. Ribosome-inactivation proteins from plants as agents for suicide transport and immunolesioning in the nervous system. Eur J Neurosci 1993;5:1292–1301.

    Article  PubMed  CAS  Google Scholar 

  15. Wiley RG, Oeltmann TN, Lappi DA. Immunolesioning: selective destruction of neurons using immunotoxin to rat NGF receptor. Brain Res 1991;562:149–153.

    Article  PubMed  CAS  Google Scholar 

  16. Stirpe F, Gasperi-Campani A, Barbieri L, Falasca A, Abbondanza A, Stevens WA. Ribosome inactivating proteins from the seeds of Saponaria officinalis L. (soapwort), of Agrostemma githago L. (corn cockle) and of Asparagus officinalis L. (asparagus), and from the latex of Hura crepitans L. (sandbox tree). Biochem J 1983;216:617–625.

    PubMed  CAS  Google Scholar 

  17. Lappi DA, Esch FS, Barbieri L, Stirpe F, Soria M. Characterization of a Saponaria officinalis seed ribosome-inactivating protein: immunoreactivity and sequence homologies. Biochem Biophys Res Commun 1985;129:934–942.

    Article  PubMed  CAS  Google Scholar 

  18. Taniuchi M, Johnson EM Jr. Characterization of the binding properties and retrograde axonal transport of a monoclonal antibody directed against the rat nerve growth factor receptor. J Cell Biol 1985;101:1100–1106.

    Article  PubMed  CAS  Google Scholar 

  19. Schweitzer JB. Nerve growth factor receptor-mediated transport from CSF labels cholinergic neurons: direct demonstration by a double-labeling study. Brain Res 1989;490:390–396.

    Article  PubMed  CAS  Google Scholar 

  20. Schweitzer JB. Nerve growth factor receptor-mediated transport from cerebrospinal fluid to basal forebrain neurons. Brain Res 1987;423:309–317.

    Article  PubMed  CAS  Google Scholar 

  21. Stirpe F, Bailey S, Miller SP, Bodley JW. Modification of ribosomal RNA by ribosome-inactivating proteins from plants. Nucleic Acids Res 1988;16:1349–1357.

    Article  PubMed  CAS  Google Scholar 

  22. Davis TL, Wiley RG. Anti-Thy-1 immunotoxin, OX7-saporin, destroys cerebellar Purkinje cells after intraventricular injection in rats. Brain Res 1989;504:216–222.

    Article  PubMed  CAS  Google Scholar 

  23. Gonzalez AM, Lappi DA, Buscaglia ML, Carman LS, Gage FH, Baird A. Basic FGF-SAP mitotoxin in the hippocampus. Specific lethal effect on cells expressing the basic FGF receptor. Ann NY Acad Sci 1991;638:442–444.

    Article  PubMed  CAS  Google Scholar 

  24. Lappi DA, Martineau D, Baird A. Biological and chemical characterization of basic FGF-saporin mitotoxin. Biochem Biophys Res Commun 1989;160:917–923.

    Article  PubMed  CAS  Google Scholar 

  25. Waite JJ, Wardlow ML, Chen AC, Lappi DA, Wiley RG, Thal LJ. Time course of cholinergic and monoaminergic changes in rat brain after immunolesioning with 192 IgG-saporin. Neurosci Lett 1994;169:154–158.

    Article  PubMed  CAS  Google Scholar 

  26. Fonnum F. Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. J Biochem 1969;115:465–479.

    CAS  Google Scholar 

  27. Waite JJ, Chen AD, Wardlow ML, Thal LJ. Behavioral and biochemical consequences of combined lesions of the medial septum/diagonal band and nucleus basalis in the rat when ibotenic acid, quisqualic acid, and AMPA are used. Exp Neurol 1994;130:214–229.

    Article  PubMed  CAS  Google Scholar 

  28. Nilsson OG, Leanza G, Rosenblad C, Lappi DA, Wiley RG, Björklund A. Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system. NeuroReport 1992;3:1005–1008.

    Article  PubMed  CAS  Google Scholar 

  29. Book AA, Wiley RG, Schweitzer JB. Specificity of 192 IgG-saporin for NGF receptor-positive cholinergic basal forebrain neurons in the rat. Brain Res 1992;590:350–355.

    Article  PubMed  CAS  Google Scholar 

  30. Waite JJ, Chen AD, Wardlow ML, Wiley RG, Lappi DA, Thal LJ. 192 immunoglobulin G-saporin produces graded behavioral and biochemical changes accompanying the loss of cholinergic neurons of the basal forebrain and cerebellar Purkinje cells. Neuroscience 1995;65:463–476.

    Article  PubMed  CAS  Google Scholar 

  31. Walsh TJ, Kelly RM, Dougherty KD, Stackman RW, Wiley RG, Kutscher CL. Behavioral and neurobiological alterations induced by the immunotoxin 192-IgG-saporin: cholinergic and non-cholinergic effects following icv injection. Brain Res 1995;702:233–245.

    Article  PubMed  CAS  Google Scholar 

  32. Lee MG, Chrobak JJ, Sik A, Wiley RG, Buzsáki G. Hippocampal theta activity following selective lesion of the septal cholinergic system. Neuroscience 1994;62:1033–1047.

    Article  PubMed  CAS  Google Scholar 

  33. Torres EM, Perry TA, Blokland A, et al. Behavioural, histochemical, and biochemical consequences of selective immunolesions in discrete regions of the basal forebrain cholinergic system. Neuroscience 1994;63:95–122.

    Article  PubMed  CAS  Google Scholar 

  34. Heckers S, Ohtake T, Wiley FG, Lappi DA, Geula C, Mesulam MM. Complete and selective cholinergic denervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor. J Neurosci 1994;14:1271–1289.

    PubMed  CAS  Google Scholar 

  35. Berger-Sweeney J, Heckers S, Mesulam MM, Wiley RG, Lappi DA, Sharma M. Differential effects on spatial navigation of immunotoxin-induced cholinergic lesions of the medial septal area and nucleus basalis magnocellularis. J Neurosci 1994;14:4507–4519.

    PubMed  CAS  Google Scholar 

  36. Wenk GL, Stoehr JD, Quintana G, Mobley S, Wiley RG. Behavioral, biochemical, histological, and electrophysiological effects of 192 IgG-saporin injections into the basal forebrain of rats. J Neurosci 1994;14:5986–5995.

    PubMed  CAS  Google Scholar 

  37. Wiley RG. Neural lesioning with ribosome inactivating proteins: suicide transport and immunolesioning. Trends Neurosci 1992;15:285–290.

    Article  PubMed  CAS  Google Scholar 

  38. Waite JJ, Wardlow ML, Power AE. Attention deficit associated with cholinergic basal forebrain immunotoxin lesion produced by 192-saporin; motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin. Neurobiol Learn Mem 1999;71:325–352.

    Article  PubMed  CAS  Google Scholar 

  39. Holley LA, Wiley RG, Lappi DA, Sarter M. Cortical cholinergic deafferentation following the intracortical infusion of 192 IgG-saporin: a quantitative histochemical study. Brain Res 1994;663:277–286.

    Article  PubMed  CAS  Google Scholar 

  40. Steckler T, Keith AB, Wiley RG, Sahgal A. Cholinergic lesions by 192 IgG-saporin and short-term recognition memory: role of the septohippocampal projection. Neuroscience 1995;66:101–114.

    Article  PubMed  CAS  Google Scholar 

  41. Ohtake T, Heckers S, Wiley RG, Lappi DA, Mesulam MM, Geula C. Retrograde degeneration and colchicine protection of basal forebrain cholinergic neurons following hippocampal injections of an immunotoxin against the P75 nerve growth factor receptor. Neuroscience 1997;78:123–133.

    Article  PubMed  CAS  Google Scholar 

  42. Winkler J, Connor DJ, Frautschy SA, et al. Lack of long-term effects after β-amyloid protein injections in rat brain. Neurobiol Aging 1994;15:601–607.

    Article  PubMed  CAS  Google Scholar 

  43. Dougherty KD, Salat D, Walsh TJ. Intraseptal injection of the cholinergic immunotoxin 192-IgG saporin fails to disrupt latent inhibition in a conditioned taste aversion paradigm. Brain Res 1996;736:260–269.

    Article  PubMed  CAS  Google Scholar 

  44. Bannon AW, Curzon P, Gunther KL, Decker MW. Effects of intraseptal injection of 192-IgG-saporin in mature and aged Long-Evans rats. Brain Res 1996;718:25–36.

    Article  PubMed  CAS  Google Scholar 

  45. McGaughy J, Kaiser T, Sarter M. Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density. Behav Neurosci 1996;110:247–265.

    Article  PubMed  CAS  Google Scholar 

  46. Chiba AA, Bucci DJ, Holland PC, Gallagher M. Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing. J Neurosci 1995;15:7315–7322.

    PubMed  CAS  Google Scholar 

  47. Pizzo DP, Waite JJ, Thal LJ, Winkler J. Intraparenchymal infusions of 192 IgG-saporin: development of a method for selective and discrete lesioning of cholinergic basal forebrain nuclei. J Neurosci Methods 1999;91:9–19.

    Article  PubMed  CAS  Google Scholar 

  48. Baxter MG, Bucci DJ, Gorman LK, Wiley RG, Gallagher M. Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats. Behav Neurosci 1995;109:714–722.

    Article  PubMed  CAS  Google Scholar 

  49. Bartus RT, Dean RL, Pontecorvo MJ, Flicker C. The cholinergic hypothesis: a historical overview, current perspective, and future directions. Ann NY Acad Sci 1985;444:332–358.

    Article  PubMed  CAS  Google Scholar 

  50. Dunnett SB, Everitt BJ, Robbins TW. The basal forebrain-cortical cholinergic system: interpreting the functional consequences of excitotoxic lesions. Trends Neurosci 1991;14:494–501.

    Article  PubMed  CAS  Google Scholar 

  51. Winkler J, Ramirez GA, Thal LJ, Waite JJ. Nerve growth factor (NGF) augments cortical and hippocampal cholinergic functioning after p 75 NGF receptor-mediated deafferentation but impairs inhibitory avoidance and induces fear-related behavior. J Neurosci 2000;20:834–844.

    PubMed  CAS  Google Scholar 

  52. Baxter MG, Gallagher M. Intact spatial learning in both young and aged rats following selective removal of hippocampal cholinergic input. Behav Neurosci 1996;110:460–467.

    Article  PubMed  CAS  Google Scholar 

  53. Dornan WA, McCampbell AR, Tinkler GP, et al. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG-saporin. Behav Brain Res 1996;82:247–265.

    Article  Google Scholar 

  54. Pizzo DP, Thal LJ, Winkler J. Mnemonic deficits in animals depend upon the degree of cholinergic deficit and task complexity. Exp Neurol 2002;177:292–305.

    Article  PubMed  CAS  Google Scholar 

  55. Sahakian BJ, Owen AM, Morant NJ, et al. Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer’s disease: assessment of attentional and mnemonic function using CANTAB. Psychopharmacology 1993;110:395–401.

    Article  PubMed  CAS  Google Scholar 

  56. Carli M, Robbins TW, Evenden JL, Everitt BJ. Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 1983;9:361–380.

    Article  PubMed  CAS  Google Scholar 

  57. Robbins TW, Everitt BJ, Marston HM, Wilkinson J, Jones GH, Page KJ. Comparative effects of ibotenic acid-and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes. Behav Brain Res 1989;35:221–240.

    PubMed  CAS  Google Scholar 

  58. Muir JL, Everitt BJ, Robbins TW. Reversal of visual attentional dysfunction following lesions of the cholinergic basal forebrain by physostigmine and nicotine but not by the 5-HT3 receptor antagonist, ondansetron. Psychopharmacology 1995;118:82–92.

    Article  PubMed  CAS  Google Scholar 

  59. Turchi J, Sarter M. Cortical acetylcholine and processing capacity: effects of cortical cholinergic deafferentation on crossmodal divided attention in rats. Brain Res Cogn Brain Res 1997;6:147–158.

    Article  PubMed  CAS  Google Scholar 

  60. Baxter MG, Holland PC, Gallagher M. Disruption of decrements in conditioned stimulus processing by selective removal of hippocampal cholinergic input. J Neurosci 1997;17:5230–5236.

    PubMed  CAS  Google Scholar 

  61. Baxter MG, Bucci DJ, Holland PC, Gallagher M. Impairments in conditioned stimulus processing and conditioned responding after combined selective removal of hippocampal and neocortical cholinergic input. Behav Neurosci 1999;113:486–495.

    Article  PubMed  CAS  Google Scholar 

  62. Zhang ZJ, Berbos TG, Wrenn CC, Wiley RG. Loss of nucleus basalis magnocellularis, but not septal, cholinergic neurons correlates with passive avoidance impairment in rats treated with 192-saporin. Neurosci Lett 1996;203:214–218.

    Article  PubMed  CAS  Google Scholar 

  63. Waite JJ, Wardlow ML, Power AE. Deficit in selective and divided attention associated with cholinergic basal forebrain immunotoxic lesion produced by 192-saporin; motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin. Neurobiol Learn Mem 1999;71:325–352.

    Article  PubMed  CAS  Google Scholar 

  64. Gandhi CC, Kelly RM, Wiley RG, Walsh TJ. Impaired acquisition of a Morris water maze task following selective destruction of cerebellar Purkinje cells with OX7-saporin. Behav Brain Res 2000;109:37–47.

    Article  PubMed  CAS  Google Scholar 

  65. Roßbner S, Yu J, Pizzo D, et al. Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion. J Neurosci Res 1996;45:40–56.

    Article  Google Scholar 

  66. Lapchak PA, Jenden DJ, Hefti F. Compensatory elevation of acetylcholine synthesis in vivo by cholinergic neurons surviving partial lesions of the septohippocampal pathway. J Neurosci 1991;11:2821–2828.

    PubMed  CAS  Google Scholar 

  67. Waite JJ, Chen AD. Differential changes in rat cholinergic parameters subsequent to immunotoxic lesion of the basal forebrain nuclei. Brain Res 2001;918:113–120.

    Article  PubMed  CAS  Google Scholar 

  68. Jenden DJ, Choi L, Silverman RW, Steinborn JA, Roch M, Booth RA. Acetylcholine turnover estimation in brain by gas chromatography/mass spectrometry. Life Sci 1974;14:55–63.

    Article  PubMed  CAS  Google Scholar 

  69. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.

    PubMed  CAS  Google Scholar 

  70. Leanza G, Nilsson OG, Bjorklund A. Compensatory changes of in vivo acetylcholine and noradrenaline release in the hippocampus after partial deafferentation, as monitored by microdialysis. Brain Res 1993;615:147–159.

    Article  PubMed  CAS  Google Scholar 

  71. Lapchak PA, Araujo DM, Pasinetti G, Hefti F. Differential alterations of cortical cholinergic and neurotensin markers following ibotenic acid lesions of the nucleus basalis magnocellularis. Brain Res 1993;613:239–246.

    Article  PubMed  CAS  Google Scholar 

  72. Wenk GL, Olton DS. Recovery of neocortical choline acetyltransferase activity following ibotenic acid injection into the nucleus basalis of Meynert in rats. Brain Res 1984;293:184–186.

    Article  PubMed  CAS  Google Scholar 

  73. Watson M, Vickroy TW, Fibiger HC, Roeske WR, Yamamura HI. Effects of bilateral ibotenate-induced lesions of the nucleus basalis magnocellularis upon selective cholinergic biochemical markers in the rat anterior cerebral cortex. Brain Res 1985;346:387–391.

    Article  PubMed  CAS  Google Scholar 

  74. Vickroy TW, Watson M, Leventer SM, Roeske WR, Hanin I, Yamamura HI. Regional differences in ethylcholine mustard aziridinium ion (AF64A)-induced deficits in presynaptic cholinergic markers for the rat central nervous system. J Pharmacol Exp Ther 1985;235:577–582.

    PubMed  CAS  Google Scholar 

  75. Scremin OU, Rovere AA, Raynald AC, Giardini A. Cholinergic control of blood flow in the cerebral cortex of the rat. Stroke 1973;4:232–239.

    CAS  Google Scholar 

  76. Biesold D, Inannami O, Sato A, Sato Y. Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci Lett 1989;98:39–44.

    Article  PubMed  CAS  Google Scholar 

  77. Lacombe P, Sercombe R, Verrecchia C, Philipson V, MacKenzie ET, Seylaz J. Cortical blood flow increases induced by stimulation of the substantia innominata in the unanesthetized rat. Brain Res 1989;491:1–14.

    Article  PubMed  CAS  Google Scholar 

  78. Scremin OU, Torres C, Scremin AME, O’Neal M, Heuser D, Blisard KS. Role of nucleus basalis in cholinergic control of cortical blood flow. J Neurosci Res 1991;28:382–390.

    Article  PubMed  CAS  Google Scholar 

  79. Santos-Benito FF, Gonzalez JL, de la Torre F. Choline acetyltransferase activity in the rat brain cortex homogenate, synaptosomes, and capillaries after lesioning the nucleus basalis magnocellularis. J Neurochem 1988;50:395–399.

    Article  PubMed  CAS  Google Scholar 

  80. Namba H, Irie T, Fukushi K, Yamasaki T, Tateno Y, Hasegawa S. Lesion of the nucleus basalis magnocellularis does not affect cerebral cortical blood flow in rats. Neurosci Res 1991;12:463–467.

    Article  PubMed  CAS  Google Scholar 

  81. Peruzzi P, Lacombe P, Moro V, Vaucher E, Levy F, Seylaz J. The cerebrovascular effects of physostigmine are not mediated through the substantia innominata. Exp Neurol 1993;122:319–326.

    Article  PubMed  CAS  Google Scholar 

  82. Barbelivien A, Noel C, MacKenzie ET, Dauphin F. Cerebrovascular evidence for a GABAergic modulation of the cholinergic vasodilatatory basalocortical system in the rat. Brain Res 1999;834:223–227.

    Article  PubMed  CAS  Google Scholar 

  83. Waite JJ, Holschneider DP, Scremin OU. Selective immunotoxin-induced cholinergic deafferentiation alters blood flow distribution in the cerebral cortex. Brain Res 1999;818:1–11.

    Article  PubMed  CAS  Google Scholar 

  84. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L. Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol Heart Circ Physiol 1978;3:H59–H66.

    Google Scholar 

  85. Nakai M, Ogata J, Fukui K, Nakai Y, Maeda M. Basal forebrain and cerebral cortical muscarinic receptors mediate increase in cortical blood flow provoked by periaqueductal gray matter. Neuroscience 1997;79:571–579.

    Article  PubMed  CAS  Google Scholar 

  86. Vaucher E, Borredon J, Seylaz J, Lacombe P. Autoradiographic distribution ofcerebral blood flow increases elicited by stimulation of the nucleus basalis magnocellularis in the unanesthetized rat. Brain Res 1995;691:57–68.

    Article  PubMed  CAS  Google Scholar 

  87. Chedotal A, Umbriaco D, Descarries L, Hartman BK, Hamel E. Light and electron microscopic immunocytochemical analysis of the neurovascular relationships of choline acetyltransferase and vasoactive intestinal polypeptide nerve terminals in the rat cerebral cortex. J Comp Neurol 1994;343:57–71.

    Article  PubMed  CAS  Google Scholar 

  88. Elhusseiny A, Cohen Z, Olivier A, Stanimirovic D, Hamel E. Functional acetylcholine muscarinic receptor subtypes in human brain microcirculation: identification and cellular localization. J Cereb Blood Flow Metab 1999;19:794–802.

    Article  PubMed  CAS  Google Scholar 

  89. Sato A, Sato Y. Cholinergic neural regulation of regional cerebral blood flow. Alzheimer Dis Assoc Disord 1995;9:28–38.

    Article  PubMed  CAS  Google Scholar 

  90. Mielke R, Schroder R, Fink GR, Kessler J, Herholz K, Heiss W-D. Regional cerebral glucose metabolism and postmortem pathology in Alzheimer’s disease. Acta Neuropathol 1996;91:174–179.

    Article  PubMed  CAS  Google Scholar 

  91. Hirsch C, Bartenstien P, Minoshima S, et al. Reduction of regional cerebral blood flow and cognitive impairment in patients with Alzheimer’s disease: evaluation of an observer-independent analytic approach. Dementia Geriatr Cogn Disord 1997;8:98–104.

    Article  CAS  Google Scholar 

  92. Herholz K, Bauer B, Wienhard K, et al. In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism. J Neural Transm 2000;107:1457–1468.

    Article  PubMed  CAS  Google Scholar 

  93. Butt AE, Bowman TD. Transverse patterning reveals a dissociation of simple and configural association learning abilities in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis. Neurobiol Learn Mem 2002;77:211–233.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of California, San Diego, CA

    Jerene J. Waite

  2. Veteran’s Medical Research Foundation, San Diego, CA

    Jerene J. Waite

Authors
  1. Jerene J. Waite
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN

    Ronald G. Wiley MD, PhD

  2. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN

    Ronald G. Wiley MD, PhD

  3. Neurology Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN

    Ronald G. Wiley MD, PhD

  4. Advanced Targeting Systems, San Diego, CA

    Douglas A. Lappi PhD (President and Chief Scientific Officer) (President and Chief Scientific Officer)

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Waite, J.J. (2005). Biochemical, Physiological, and Behavioral Characterizations of the Cholinergic Basal Forebrain Lesion Produced by 192 IgG-Saporin. In: Wiley, R.G., Lappi, D.A. (eds) Molecular Neurosurgery With Targeted Toxins. Humana Press. https://doi.org/10.1007/978-1-59259-896-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-896-0_3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-199-8

  • Online ISBN: 978-1-59259-896-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation