Development and Aging of Cholinergic Synapses

Abstract

Age-related changes in the activities of choline acetyltransferase and acetylcholinesterase in avian sympathetic ganglia, ciliary ganglia and iris have been determined throughout the posthatching life span. Kinetic characteristics of these enzymes have been analyzed in the nerve terminals in the iris from early embryonic stages to the latest periods of life. Enzyme activities and kinetics have been related to each other and also to the endogenous levels of acetylcholine. The regulation of the biosynthetic mechanism for acetylcholine through choline uptake and choline acetyltransferase activity in the developing nerve terminal have been examined. The activities of both enzymes in all tissues are reduced at later ages, which is referred to declines in V_max, as the K_m values do not vary significantly at any age. Declines with age are most pronounced in the iris, both in choline acetyltransferase activity and V_max and in acetylcholine levels, supporting our view of the peripheral autonomic nerve terminal as a major locus for the effects of aging on the peripheral nervous system.

Innovative Therapy for Alzheimer’s Disease-With Focus on Biodelivery of NGF

“…Presently, the only available treatment option is the use of drugs called cholinesterase inhibitors (ChEIs, which includes donepezil, rivastigmine, and galantamine) and glutamate receptor (NMDA) antagonist (memantine). Activity of acetylcholinesterase in central nerve cells was observed a few decades back leading to large research efforts to therapeutically target them for modifications of the cholinergic pathways in AD (Giacobini and Zajicek, 1956; Marchi et al, 1980; De Sarno et al, 1989; Giacobini et al, 1989; Messamore et al, 1993a,b; Zhu and Giacobini, 1995; Giacobini, 1998, 2004; Taylor, 1998). These drugs provide symptomatic relief and temporarily stabilize cognitive functions, without any impact on disease progression or severity (Rodda and Carter, 2012; Deardorff et al, 2015).…”