Can Septal Grafting Facilitate Recovery from Physiological and Behavioral Deficits Produced by Fornix Transections?
There is now considerable evidence which links the severe memory deficit of dementia of the Alzheimer type (AD) to degeneration of cholinergic basal forebrain neurons and a corresponding reduction in forebrain acetylcholine (ACh) (1–5), The significance of such correlations are strengthened by observations of memory deficits in animals produced by either pharmacological blocking of ACh or by specific brain lesions (6). In spite of this evidence, attempts to alleviate memory deficits in AD patients by pharmacological manipulation of acetylcholine has had only limited success (7). It is consequently of considerable importance to evaluate the feasibility of treating cognitive dysfunctions by other means such as the recently developed procedure of grafting fetal neural tissue into adult hosts (8,9,10). The present studies were undertaken with this purpose in mind. We have been studying the effects of grafted cholinergic neurons on an animal model of AD produced by denervation of the cholinergic input of the hippocampus.
KeywordsAttenuation Dementia Syringe Cholin Acetylcholine
Unable to display preview. Download preview PDF.
- 1.E.K. Perry, R.H. Perry, P.H. Gibson, G. Blessed and B.E. Tomlinson, A cholinergic connection between normal aging and senile dementia in the human hippocampus, Neurosc. Lett. 3:88 (1977).Google Scholar
- 2.E.K. Perry, B.E. Tomlinson, G. Blessed, K. Bergmann, P.H. Gibson and R.H. Perry, Correlation of cholinergic abnormalities with senile plaques and mental test scores in senila dementia, Br. Med. J. 2:1457 (1978).Google Scholar
- 6.J. O’Keefe and L. Nadel, The hippocampus as a cognitive map, Clarendon Press, Oxford, 1978.Google Scholar
- 7.S. Corkin, K.L. Davis, J.H. Growdon, E. Usdin and R.J. Wurtman, Alzheimer’s disease: a report of progress in research, Raven Press, N.Y. (1982).Google Scholar
- 8.A. Bjttrklund, F.H, Gage, U. Stenevi and S.B. Dunnett, Survival andgrowth of intrahippocampal implants of septal cell suspensions, Acta Physiol. Scand. Suppl. 522:49 (1983).Google Scholar
- 9.A. Bjttrklund, U. Stenevi, R.H. Schmidt, S.B. Dunnett and F.H. Gage, Introduction and general methods of preparation, Acta Physiol. Scand. Suppl. 522:1 (1983).Google Scholar
- 11.K. Krnjevic, R. Pumain and L. Renaud, The mechanism of excitation by acetylcholine in the cerebral cortex, J. Physiol. (Lond.) 215:247 (1971).Google Scholar
- 15.G. G. Buzsaki, L.W.S. Leung and C.H. Vanderwolf, Cellular bases of hippocampal EEG in the behaving rat, Brain Res. Reviews 6:139 (1983).Google Scholar
- 16.C.H. Vanderwolf, R. Kramis, L.A. Gillespie and B.H. Bland, Hippocampal slow activity and neocortical low voltage fast activity: relations to behavior, in: “The Hippocampus”, Vol. 2, R.L. Issac- son and K. Pribram, eds., Plenum Press, N.Y. (1975).Google Scholar
- 17.H. Petsche, C.H. Stumpf and G. Gogolak, The significance of the rabbit’s septum as a relay station between the midbrain and the hippocampus. I. Control of hippocampal arousal activity by the septum cells. Electroencephalog. Clin. Neurophysiol. 14:202 (1962).Google Scholar
- 18.O. Macadar, J.A. Roig, J.M. Monti and R. Budelli, The functional relationship between septal and hippocampal unit activity and hippocampal theta rhythm, Physiol. Behav. 5:1443 (1970).Google Scholar
- 24.M. Segal, A. Bjttrklund and F.H. Gage, Transplanted septal neurons make viable cholinergic synapses with a host hippocampus, Brain Res. (1985) in press.Google Scholar
- 25.F.H. Gage, S.B. Dunnett, U. Stenevi and A. Bjttrklund, Aged rats:recovery of motor impairments by intrastriatal nigral grafts, Science 221:966 (1983).Google Scholar
- 27.R. Morris, Developments of a water-maze procedure for studying spatial learning in the rat, J. Neurosci. Methods 11:47–60 (1984).Google Scholar