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Animal Models of Alzheimer's Disease: Behavior, Pharmacology, Transplants

Published online by Cambridge University Press:  18 September 2015

V. Haroutunian ,
P.D. Kanof ,
G.K. Tsuboyama ,
G.A. Campbell  and
K.L. Davis
V. Haroutunian*
Affiliation:
Bronx VA Medical Center and The Mount Sinai School of Medicine, Bronx, New York
P.D. Kanof
Affiliation:
Bronx VA Medical Center and The Mount Sinai School of Medicine, Bronx, New York
G.K. Tsuboyama
Affiliation:
Bronx VA Medical Center and The Mount Sinai School of Medicine, Bronx, New York
G.A. Campbell
Affiliation:
Bronx VA Medical Center and The Mount Sinai School of Medicine, Bronx, New York
K.L. Davis
Affiliation:
Bronx VA Medical Center and The Mount Sinai School of Medicine, Bronx, New York
*
Psychiatry Service, Bronx VA Medical Center, 130 W. Kingsbridge Road, Bronx, N.Y., U.S.A. 10468
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Abstract:

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Physostigmine, oxotremorine, RS-86, and a combination of piracetam and lecithin, have all been studied in patients with Alzheimer's disease. Intravenous physostigmine produced a significant improvement in patients' ability to recognize words and particularly to distinguish words they had never seen before from words previously presented. A subgroup of Alzheimer's patients had a clinically meaningful improvement to treatment with oral physostigmine, with the degree of improvement correlating with the ability of oral physostigmine to increase the nocturnal secretion of Cortisol. No statistically significant differences of piracetam or piracetam and lecithin, compared to placebo were noted, however, the ratio of red cell to plasma choline might be associated with treatment responsivity. The potential therapeutic efficacy of oxotremorine proved all but impossible to assess due to concomitant adverse effects, particularly dysphoria. Results with another cholinergic agonist, RS-86, will be reported. This drug appeared to be better tolerated than oxotremorine.

Animals with a kianic acid induced cortical depletion of choline acetyltransferase were found to have a significant impairment in retention of a passive avoidance task, an abnormality that was readily reversible by physostigmine, oxotremorine and 4-amino-pyridine. Cysteamine, a depletor of somatostatin, also produced a comparable deficit.

Type
Clinical and Therapeutic Issues
Information
Canadian Journal of Neurological Sciences , Volume 13 , Issue S4 , November 1986 , pp. 385 - 393
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

References

1.Whitehouse, PJ, Price, DL, Struble, RG, Clark, AW, Coyle, JT.Alzheimer’s disease and senile demenlia: loss of neurons in the basal forebrain. Science 1982; 215: 1237–1239.CrossRefGoogle ScholarPubMed
2.Candy, JM, Perry, RH, Perry, EK, Irving, D, Blessed, G, Fairbairn, , Tomlinson, RL.Pathological changes in the nucleus of Meynert in Alzheimer’s disease and Parkinson’s disease. J Neurol Science 1983; 54: 277–289.CrossRefGoogle Scholar
3.Pearson, RCA, Sofroniew, MV, Cuello, AC.Powell, TPS, Eckenstein, F, Esiri, MM, Wilcock, GK.Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of Alzheimer’s type demonstrated by immunohistochemical staining for choline acetyl-transferase. Brain Research 1983; 289: 370–374.CrossRefGoogle Scholar
4.McKinney, M, Coyle, JT, Hedeen, JC.Topographic analysis of the innervation of the rat neocortex and hippocampus by basal forebrain cholinergic system. J Comparative Neurology 1983; 217: 103–121.CrossRefGoogle ScholarPubMed
5.Johnston, MV, McKinney, M, Coyle, JT.Neocortical cholinergic innervation: A description of extrinsic and intrinsic components in the rat. Experimental Brain Research 1981; 43: 159–172.CrossRefGoogle ScholarPubMed
6.Wenk, H, Volker, B, Meyer, U.Cholinergic projections from magnocellular nuclei of the basal forebrain to cortical area in rats. Brain Research Reviews 1980; 2: 295–316.CrossRefGoogle Scholar
7.Fibiger, HC.The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Research Reviews 1982; 4: 327–388.CrossRefGoogle Scholar
8.Davies, P, Maloney, AJF.Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976; 2: 1403.CrossRefGoogle ScholarPubMed
9.Perry, EK, Perry, RH, Blessed, G, Tomlinson, BE.Necropsy evidence of central cholinergic deficits in senile dementia. Lancet 1976; 2: 143.Google Scholar
10.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. British Medical Journal 1978; 2: 1457–1459.CrossRefGoogle ScholarPubMed
11.Bartus, RT, Dean, RL, Beer, B, Lippa, AS.The cholinergic hypothesis of geriatric memory dysfunction: A critical review. Science 1982;217:408–417.CrossRefGoogle Scholar
12.LoConte, G, Bartolini, L, Castamenti, F, Marconcini-Pepeu, I, Pepeu, G.Lesions of cholinergic forebrain nuclei: Changes in avoidance behavior and scopolamine action. Pharmacology Biochemistry and Behavior 1982; 17: 933–937.CrossRefGoogle Scholar
13.Flicker, C, Dean, RL, Watkins, DL, Fisher, SK, Bartus, RT.Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat. Pharmacology Biochemistry and Behavior 1983; 18: 973–981.CrossRefGoogle Scholar
14.Altman, HJ, Crosland, RD, Jenden, DJ, Berman, RF.Further characterizations of the nature of the behavioral and neurochemical effects of lesions to the nucleus basalis of Meynert in the rat. Neurobiology of Aging 1985; 6: 125–130.CrossRefGoogle Scholar
15.Haroutunian, V, Kanof, P, Davis, KL.Pharmacological alleviation of cholinergic lesion induced memory deficits in rats. Life Sciences 1985; 945–952.CrossRefGoogle ScholarPubMed
17.Bartus, RT, Pontecorvo, M, Flicker, C, Dean, RL, Figueiredo, JC.Behavioral recovery following bilateral lesions of the nucleus basalis does not occur spontaneously. Pharmacology, Biochemistry and Behavior 1986; 24: 1287–1292.CrossRefGoogle Scholar
18.Wenk, GL, Olton, DS.Recovery of neocortical choline acetyltransferase activity following ibotenic acid injection into the nucleus basalis of Meynert in rats. Brain Research 1984; 293: 184–186.CrossRefGoogle ScholarPubMed
19.Bartus, RT, Flicker, C, Dean, RL, Pontecorvo, M, Figueiredo, JC, Fisher, SK.Selective memory loss following nucleus basalis lesions: Long term behavioral recovery despite persistent cholin-ergicdeficiencies. Pharmacology, Biochemistry and Behavior 1985; 23: 125–135.CrossRefGoogle Scholar
20.Salamone, JD, Beart, PM, Alpert, JE, Iversen, SD.Impairment in T-maze alternation following nucleus basalis magnocellularis lesions in rats. Behavioral Brain Research 1984; 13: 63–70.CrossRefGoogle ScholarPubMed
21.Murray, CL, Fibiger, HC.Learning and memory deficits after lesions of the nucleus basalis magnocellularis: Reversal by Physostigmine. Neuroscience 1985; 19: 1025–1032.CrossRefGoogle Scholar
22.Murray, CL, Fibiger, HC.Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis. Behavioral Neuroscience 1986; 100: 23–32.CrossRefGoogle ScholarPubMed
23.Beal, MF, Mazurek, MF, Tran, VT, Chattha, G, Bird, ED, Martin, JB.Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer’s disease. Science 1985; 229: 289–291.CrossRefGoogle ScholarPubMed
24.Davies, P, Katzman, R,Terry, RD.Reducedsomatostatin-likeimmunoreactivity in cerebral cortex from cases of Alzheimer’s disease Alzheimer senile dementia. Nature 1980; 288: 279–280.CrossRefGoogle Scholar
25.Rossor, MN, Emson, PC, Mountjoy, CQ, Roth, M, Iversen, LL.Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer’s type. Neuroscience Letters 1980; 20: 373–377.CrossRefGoogle Scholar
26.Bennett-Clarke, C, Romagnano, MA, Joseph, SA.Distribution of somatostatin in the rat brain: telencephalon and diencephalon. Brain Research 1980; 188: 473–486.CrossRefGoogle ScholarPubMed
27.Johansson, O, Hokfelt, T, Elde, RP.Immunohistochemical distribution of somatostatin-like-immunoreactivity in the central nervous system of the rat. Neuroscience 1984; 13: 265–339.CrossRefGoogle Scholar
28.Haroutunian, V, Mantin, R, Campbell, GA, Tsuboyama, GK, Davis, KL.Cysteamine-induced depletion of central somatostatin-like immunoactivity: Effects on behavior, learning, memory and brain neurochemistry. Brain Research (in press).Google Scholar
29.DiLiberato, EJ, Distefano, V, Smith, JC.Mechanisms and kinetics of the inhibition of dopamine-B-hydroxylase by 2-mercapto-ethylguanidine. Biochemical Pharmacology 1973;22:2961–2972.CrossRefGoogle Scholar
30.Vecsei, L, Kiraly, C, Bollok, I, Nagy, A, Verga, J, Penke, B, Telegdy, G.Comparative studies with somatostatin and cysteamine in different behavioral tests on rats. Pharmacology, Biochemistry and Behavior 1984; 21: 833–837.CrossRefGoogle ScholarPubMed
31.Bakhit, C, Swerdlow, NR.Behavioral changes following central injection of cysteamine in rats. Soc Neuroscience Abst 1984; 10: 182.Google Scholar
32.Cutler, NR, Haxby, JV, Narang, PK, May, C, Burg, C, Reines, SA.Evaluation of an analogue of somatostatin (L363, 586) in Alzheimer’s disease. New England J Medicine 1985; 312: 725.Google ScholarPubMed
33.Adolfsson, R, Gottfries, CG, Roos, BE, Winblat, B.Changes in the brain catecholamines in patients with dementia of Alzheimer’s type. British J Psychiatry; 1979: 135: 216–223.CrossRefGoogle Scholar
34.Benton, JS, Bowen, DM, Allen, SJ, Haan, EA, Davison, N, Neary, D, Murphy, RP, Snowden, JS.Alzheimer’s disease as a disorder of isodendritic core. Lancet 1982; 20: 456.CrossRefGoogle Scholar
35.Perry, EK, Tomlinson, BE, Blessed, G, Perry, RH, Cross, AJ, Crow, TJ.Neuropathological and biochemical observations on the noradrenergic system in Alzheimer’s disease. J Neurol Science 1981;51: 279–337.CrossRefGoogle ScholarPubMed
36.Mason, ST.Noradrenaline in the brain: Progress in theories of behavioral function. Progressin Neurobiology 1981; 16:262–303.Google Scholar
37.McNaughton, N, Mason, ST.The neuropsychology and neuropharmacology of the dorsal ascending noradrenergic bundle- A review. Progress in Neurobiology 1980; 14: 157–219.CrossRefGoogle ScholarPubMed
38.Gold, PE, Zometzer, SF.The mnemon and itsjuices: Neuromodulation of memory processes. Behavioral and Neural Biology 1983; 38: 151–189.CrossRefGoogle ScholarPubMed
39.Glavin, GB.Stress and brain noradrenaline: A review. Neuroscience and Biobehavioral Reviews 1985; 9: 233–243.Google Scholar
40.Mason, ST.Noradrenaline: Reward or extinction? Neuroscience & Biobehavioral Reviews 1979; 3: 1–10.CrossRefGoogle Scholar
41.Mason, ST, Fibiger, HC.6-OHDA lesions of the dorsal noradrenergic bundle alters extinction of passive avoidance. Brain Research 1978; 152: 209–214.CrossRefGoogle ScholarPubMed
42.Mason, ST, Iversen, SD.Effects of selective forebrain noradrenaline loss on behavioral inhibition in the rat. J Comparative and Physiological Psychology 1977; 91: 165–173.CrossRefGoogle ScholarPubMed
43.Chrobak, JJ, Dehaven, DL, Walsh, TJ.Depletion of brain noradrenaline with DSP-4 does not alter acquisition or performance of a radial-arm maze task. Behavioral and Neural Biology 1985; 44: 144–150.CrossRefGoogle ScholarPubMed
44.Mason, ST, Fibiger, HC.Noradrenaline and spatial memory. Brain Research 1978; 156: 382–386.CrossRefGoogle ScholarPubMed
45.Arnstein, AFT, Goldman-Rakic, PS.Catecholamines and cognitive decline in aged nonhuman primates. Annals of the New York Academy of Sciences 1985; 444: 218–234.CrossRefGoogle Scholar
46.Goldman-Rakic, PS, Brown, RM.Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 1981; 6: 177–187.CrossRefGoogle ScholarPubMed
47.Gold, PE, Murphy, JM.Brain noradrenergic responses to training and to amnestic frontal cortex stimulation. Pharmacology, Biochemistry and Behavior 1980, 13: 257–263.CrossRefGoogle ScholarPubMed
48.Gold, PE, McGaugh, JL.Hormones and memory. In: Miller, LH, Sandman, CA, Kastin, AJ, eds. Neuropeptide Influences on the Brain and Behavior 1977; 127–143.Google ScholarPubMed
49.Welsh, KA, Gold, PE.Brain catecholamines and memory modulation: Effects of footshock, amygdala implantation, and stimulation. Behavioral and Neural Biology 1985; 43: 119–131.CrossRefGoogle ScholarPubMed
50.Gold, PE, Robertson, NL, Delanoy, RL.Post-training brain catecholamine levels: lack of response to water-motivated training. Behavioral and Neurobiology 1985; 44: 425–433.Google ScholarPubMed
51.Haroutunian, V, Riccio, DC.Effects of arousal conditions duringreinstatement treatments upon learned fear in young rats. Developmental Psychobiology 1977; 10: 25–32.CrossRefGoogle ScholarPubMed
52.Gold, PE, van Buskirk, RB.Facilitation of time-dependent memory processes with post-trialepinephrineinjections. Behavioral Biology 1975; 13: 145–153.CrossRefGoogle Scholar
53.Levy, A, Brandies, R, Dachir, S, Luz, S, Karton, Y, Heldman, E, Pittel, Z, Fisher, A.Reversal of AF64A-induced memory impairment by cholinergic compounds. Neuroscience Abstracts 1985, 11:2, 875.Google Scholar
54.Haroutunian, V, Barns, E, Davis, KL.Cholinergic modulation of memory in rats. Psychopharmacology 1985; 87: 266–271.CrossRefGoogle ScholarPubMed
55.Flood, JS, Landry, DW, Jarvik, ME.Cholinergic receptor interactions and their effects on long-term memory processing. Brain Research 1981, 215: 177–185.CrossRefGoogle ScholarPubMed
56.Flood, JS, Smith, GE, Cherkin, A.Memory retention: Potentiation of cholinergic drug combinations in mice. Neurobiology of Aging 1983; 4: 37–43.CrossRefGoogle ScholarPubMed
57.Ridley, RM, Murray, TK, Johnson, JA, Baker, HF.Learning Impairment following lesion of the basal nucleus of Meynert in marmoset: Modification by cholinergic drugs. Brain Research 1986; 376: 108–116.CrossRefGoogle ScholarPubMed
58.Mohs, RC, Davis, BM, Johns, CA, Mathe, AA, Greenwald, BS, Horvath, TB, Davis, KL.Oral physostigmine treatment of patients with AD. Amer J Psychiatry 1985; 142: 28–33.Google Scholar
59.Haroutunian, V, Davis, KL, Davis, BM, Horvath, PB, Johns, CA, Mohs, RC.The study of cholinomimetics in Alzheimer’s disease and animal models. Iversen, SD.Psychopharmacology: Recent advances and future prospects. Oxford University Press (Oxford, New York, Tokyo) 1985.Google Scholar
60.Hollander, E, Mohs, RC, Davis, KL.Cholinergic approaches to the treatment of Alzheimer’s disease. British Medical Bulletin 1986; 42: 97–100.CrossRefGoogle Scholar
61.Arai, H, Kosaka, K, lizuka, T.Changes of biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia. J Neurochemistry 1984; 43: 388–393.Google ScholarPubMed
62.Huygens, P, Baratti, CM, Gardella, JL, Filinger, E.Brain catecholamines modification. The effects on memory facilitation induced by oxotremorineinmice. Psychopharmacology 1980; 69:291–294.CrossRefGoogle Scholar
63.Mason, ST, Fibiger, HC.Possible behavioral function for noradrenaline-acetylcholine interaction in brain. Nature 1979; 277: 396–397.CrossRefGoogle ScholarPubMed
64.Waterhouse, BD, Moises, HC, Woodwark, DJ.Alpha-receptormediated facilitation of somatosensory cortical neuronal responses to excitatory synaptic inputs and iontophoretically applied acetylcholine. Neuropharmacology 1981; 20: 907–920.CrossRefGoogle ScholarPubMed
65.Vizi, ES.Modulation of cortical release of acetylcholine by noradrenaline released from nerves arising from the rat locus coeruleus. Neuroscience 1980; 5: 2139–2144.CrossRefGoogle ScholarPubMed
66.Gash, DM, Collier, TJ, Sladek, JR Jr. Neural transplantation: A review of recent developments and potential application to the aged brain. Neurobiology of Aging 1985, 6: 131–150.CrossRefGoogle Scholar
67.Dunnett, SB, Low, WC, Iversen, SD, Stenevi, U, Bjorklund, A.Septal transplants restore maze learning in rats with fornix-fimbria lesions. Brain Research 1982; 251: 335–348.CrossRefGoogle ScholarPubMed
68.Kimble, DP, Breiller, R, Stickrod, G.Fetal brain implants improvemaze performance in hippocampal-lesioned rats. Brain Research 1986; 363: 358–363.CrossRefGoogle ScholarPubMed
69.Haroutunian, V, Kanof, PD, Davis, KL.Partial behavioral, histochemical and neurochemical restoration of fimbria/fornix lesion-induced deficits by septal transplants (in review).Google Scholar
70.Dunnett, SB, Tonilo, G, Fine, A, Ryan, CN, Bjorklund, A, Iversen, SD.Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocel-lularis-Il. Sensorimotor and learning impairments. Neuroscience 1985; 16: 787–797.CrossRefGoogle Scholar
71.Fine, A, Dunnett, SB, Bjorklund, A, Iverson, SD.Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer’s disease. Proceedings of the National Academy of Science, USA 1985; 82: 5227–5229.CrossRefGoogle Scholar
72.Appel, SH.A unifying hypothesis for the causes of amyotrophic lateral sclerosis, parkinsonism and Alzheimer’s disease. Annals of Neurology 1981; 10: 499–505.CrossRefGoogle Scholar
73.Hefti, F.Is Alzheimer’s disease caused by lack of nerve growth factor? Annals of Neurology 1983; 13: 109–110.CrossRefGoogle ScholarPubMed
74.Thoenen, H, Edgar, D.Neurotrophic factors. Science 1985; 229: 238–242.CrossRefGoogle ScholarPubMed
75.Shooter, EM, Yankner, BA, Landreth, GE, Sutter, A.Biosynthesis and mechanism of action of nerve growth factor. Recent Progress in Hormone Research 1981; 37: 417–466.Google ScholarPubMed
76.Thoenen, H, Barde, Y-A.Physiology of nerve growth factor. Physiological Reviews 1980; 60: 1284–1335.CrossRefGoogle ScholarPubMed
77.Bass, NH.Ganglioside sialic acid as a quantitative neurochemical index of the integrity of synaptic function in cognitive disorders of development and aging. In: Rapport, MM, Gorio, A, eds. Gangliosides in Neurological and Neuromuscular Function, Raven Press, New York 1981; 29–42.Google Scholar
78.Hefti, F, Dravid, A, Hartikka, J.Chronic intraventricular injections of nerve growth factor elevate hippocampal choline acetyltrans-ferase activity in adult rats with partial septo-hippocampal lesions. Brain Research 1984; 293: 305–311.CrossRefGoogle Scholar
79.Mobley, WC, Rutkowski, JL, Tennekoon, GI, Buchanan, K, Johnston, MV.Choline acepy transferase activity in spriatum of neo-natal rats increased by nerve growth factor. Science 1985; 229: 284–287.CrossRefGoogle Scholar
80.Haroutunian, V, Kanof, P, Davis, KL.Partial reversal of lesioninduced deficits in cortical cholinergic markers by nerve growth factor. Brain Research (in press).Google Scholar
81.Seiler, M, Schwab, ME.Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Research 1984; 300: 33–39.CrossRefGoogle ScholarPubMed
82.Stein, DG, Will, BE.Nerve growth factor produces a temporary facilitation of recovery from entorhinal cortex lesions. Brain Research 1983,261: 127–131.CrossRefGoogle ScholarPubMed
83.Finger, S, Stein, DG.Brain damage and recovery: research and clinical perspectives. Academic Press, New York 1982; 227–256.Google Scholar
84.Sabel, BA, Slavin, MD, Stein, DG.GMI, ganglioside treatment facilitates behavioral recovery from bilateral brain damage. Science 1984; 225: 340–341.CrossRefGoogle Scholar
85.Sabel, BA, Dunbar, GL, Stein, DG.Gangliosides minimize behavioral deficits and enhance structural repair after brain injury. J Neuroscience Research 1984; 12: 429–443.CrossRefGoogle ScholarPubMed
86.Wojcik, M, Ulas, J, Oderfeld-Nowak, B.The stimulating effect of ganglioside injections on the recovery of choline acetyltransferase and acetylcholinesterase activities in the hippocampus of the rat after septal lesions. Neuroscience 1982; 7: 495–499.CrossRefGoogle ScholarPubMed
87.Oderfeld-Nowak, B, Skup, M, Ulas, J, Jezierska, M, Gradkowska, M, Zaremba, M.Effect of GMI ganglioside treatment on postlesion responses of cholinergic enzymes in rat hippocampus after various partial deafferentations. J Neuroscience Research 1984; 12: 409–420.CrossRefGoogle Scholar
88.Karpiak, SE.Ganglioside treatment improves recovery of alternation behavior after unilateral entorhinal cortex lesion. Experimental Neurology 1983; 81: 330–339.CrossRefGoogle ScholarPubMed
89.Oderfeld-Nowak, B, Wojcik, M, Ulas, J, Potempska, A.Effects of chronic ganglioside treatment on recovery processes in hippocampus after brain lesions in rats. In: Rapport, MM, Gorio, A, eds. Gangliosides in Neurological and Neuromuscular Function, Raven Press, New York 1981; 197–209.Google Scholar
90.Toffano, G, Agnati, LF, Fuxe, K, Aldina, C, Consolazione, A, Valenti, G, Savoini, G.Effect of GMI ganglioside treatment on the recovery of dopaminergic nigro-striatal neurons after different types of lesions. Acta Physiol Scand 1984; 122: 313–321.CrossRefGoogle Scholar
91.Agnati, LF, Fuxe, K, Calza, L, Benfenati, F, Cavicchioli, L, Toffano, G, Goldstein, M.Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting. Acta Physiol Scand 1983; 119: 347–363.CrossRefGoogle ScholarPubMed
92.Cuello, AC, Stephens, PH, Tagari, PC, Sofroniew, MV, Pearson RCA. Retrograde changes in the nucleus basalis of the rat, caused by cortical damage, are prevented by exogenous ganglioside GMI. Brain Research 1986; 376: 373–377.CrossRefGoogle Scholar
93.Li, YS, Mahadik, SP, Rapport, MM, Karpiak, SE.Acute effects of GMI ganglioside: Reduction in both behavioral asymmetry and loss of Na+, K+ -ATPase after nigrostriatal transection. Brain Research 1986; 377: 292–297.CrossRefGoogle Scholar