Aging-Induced Changes in the Autoregulation of Acetylcholine Release in the Rat Brain

  • B. V. Rama Sastry
  • V. E. Janson
  • O. S. Tayeb
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


Senile dementia of Alzheimer type (SDAT) is a disease of mid- or late life, and about 3 to 4% of the population above 65 years of age is estimated to be afflicted by this progressive dementia.’ One of the main characteristics of this disease is a decline in such cognitive abilities as memory and learning.’ The decline in recent memory seems to be a common characteristic of aging in mammals including humans, non-human primates, and rodents. In humans, this impairment is exacerbated by SDAT. Although the reasons for this cognitive loss in aged or demented subjects are not fully understood, there is evidence that deficits in central cholinergic transmission play an important role.1,3 Postmortem samples from cortical regions of Alzheimer’s Disease (AD) patients have shown decreases of greater than 50% in the activity of choline acetyltransferase (ChAT), the enzyme that catalyzes the final step in the synthesis of acetylcholine (ACh). Scopolamine, an anticholinergic agent, causes memory defects in young adult volunteers. Physostigmine causes memory and thinking disturbances in human volunteers by preventing the hydrolysis of ACh, which accumulates to reach inhibitory concentrations at muscarinic receptors.


Spontaneous Release Cholinergic Transmission Negative Feedback System Young Adult Volunteer Aging Cerebrum 
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  1. 1.
    B. Reisberg. “Brain Failure: An Introduction to Current Concepts of Senility, Free Press, New York (1981).Google Scholar
  2. 2.
    M.J. Ponticorvo, C. Flicker and R.T. Bartus, Cholinergic disfunction and memory: implications for the development of animal models of aging and dementia, Adv. Behay. Biol. 30: 205 (1986).Google Scholar
  3. 3.
    A. Nordberg, Biological markers and cholinergic hypothesis in Alzeheimer’s disease, Acta Neurol. Scand. (Suppl.) 139: 54 (1992).Google Scholar
  4. 4.
    Committee on animal models for research and aging, in: “Mammalian Models for Research, pp. 21179 and 291–307, National Academy Press, Washington, DC (1981).Google Scholar
  5. 5.
    B.V.R. Sastry, V.E. Janson, N. Jaiswal and O.S. Tayeb, Changes in enzymes of the cholinergic system and acetylcholine release in the cerebra of aging male Fischer rats, Pharmacology 26: 61 (1983).Google Scholar
  6. 6.
    B.V.R. Sastry and O.S. Tayeb, Regulation of acetylcholine release in the mouse cerebrum by methionine enkephalin and substance P, Adv. Biosci. 38: 165 (1982).Google Scholar
  7. 7.
    B.V.R. Sastry, N. Jaiswal, O.S. Tayeb, Regulation of acetylcholine release from rodent cerebrum by presynaptic receptors, methionine enkephalin and substance P, Adv. Behavioral Biol. 30: 1047 (1986).Google Scholar
  8. 8.
    B.V.R. Sastry, L.K. Owens and R.F. Ochillo, Two furan analogs of muscarine as selective agonists at the presynaptic muscarinic receptors of the guinea pig longitudinal ileal muscle, Ann. N.Y. Acad. Sci. 604: 566 (1990).Google Scholar
  9. 9.
    B.V.R. Sastry, O.S. Tayeb, V.E. Janson and L.K. Owens, Peptides from human placenta: methionine enkephalin and substance P, Placenta (Suppl 3 ): 328 (1981).Google Scholar
  10. 10.
    B.V.R. Sastry, V.E. Janson, L.K. Owens and O.S. Tayeb, Enkephalin-like and substance P-like immunoreactivities of mammalian sperm and accessory sex glands. Biochem. Pharmacol. 31: 3529 (1982).Google Scholar
  11. 11.
    I. Hanin, Cholinergic toxins and Alzeheimer’s disease, Ann. N.Y. Acad. Sci. 648: 63 (1992).Google Scholar
  12. 12.
    C. Kowalski, J. Micheau, R. Corder, R. Gaillard and B. Conte-Devolx, Age-related changes in cortico-releasing factor, somatostatin, neuropeptide Y, methionine enkephalin and 6-endorphin in specific rat brain areas, Brain Res. 582: 39 (1992).Google Scholar
  13. 13.
    T. Sakurada, I. Alufuzoff, B. Winblad and A. Nordberg, Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergie muscarinic receptors in Alzeheimer’s disease and multi-infarct dementia, Brain Res. 521: 329 (1990).Google Scholar
  14. 14.
    B.J. Quigley Jr. and N.W. Knowall, Substance P-like immunoreactive neurons are depleted in Alzheimer’s disease cerebral cortex, Neuroscience 41: 41 (1991).Google Scholar
  15. 15.
    C. Bouras, P.G. Vallet, P.R. Hoff, Y. Charnay, J. Golaz and J. Constantinidas, Substance P immunoreactivity in Alzeheimer’s dises«: a study in cases presenting symmetric or asymmetric cortical atrophy, Alzheimer Dis. Assoc. Disord. 4: 24 (1990).Google Scholar
  16. 16.
    R.K. Jaiswal, N. Jaiswal and B.V.R. Sastry, Age-related changes in phospholipid methylation and fluidity in microsomal and plasma membranes of the rat liver, Age 5: 137 (1982).Google Scholar
  17. 17.
    B.V.R. Sastry, L.S. Merkens and V.E. Janson, Age-related changes in the phospholipid methylation and membrane fluidity in the rat renal plasma membranes, Age 6: 140 (1983).Google Scholar
  18. 18.
    B.V.R. Sastry, Nicotinic Receptor, Anesth. Pharmacol. Rev. 1: 6 (1993).Google Scholar
  19. 19.
    J. Schnabel, New Alzeheimer’s therapy suggested, Science 260: 1719 (1993).Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • B. V. Rama Sastry
    • 1
  • V. E. Janson
    • 1
  • O. S. Tayeb
    • 1
  1. 1.Departments of Anesthesiology and PharmacologyVanderbilt University Medical CenterNashvilleUSA

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