Chronic Cerebral Ischaemia Forms New Cholinergic Mechanisms of Learning and Memory

Abstract

The purpose of this research was a comparative analysis of cholinergic synaptic organization following learning and memory in normal and chronic cerebral ischaemic rats in the Morris water maze model. Choline acetyltransferase and protein content were determined in subpopulations of presynapses of “light” and “heavy” synaptosomal fractions of the cortex and the hippocampus, and the cholinergic projective and intrinsic systems of the brain structures were taken into consideration. We found a strong involvement of cholinergic systems, both projective and intrinsic, in all forms of cognition. Each form of cognition had an individual cholinergic molecular profile and the cholinergic synaptic compositions in the ischaemic rat brains differed significantly from normal ones. Our data demonstrated that under ischaemic conditions, instead of damaged connections new key synaptic relationships, which were stable against pathological influences and able to restore damaged cognitive functions, arose. The plasticity of neurochemical links in the individual organization of certain types of cognition gave a new input into brain pathology and can be used in the future for alternative corrections of vascular and other degenerative dementias.

The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the Cholinergic System in This Phenomenon

“…At similar low concentrations, a selective agonist of the α4β2 subtype of nAChRs (RJR 2304) and an antagonist of non-α7 nAChR subtypes (mecamylamine) were able to influence the learning of normal and ischaemic rats following subchronic systemic administration [64]. This study used two doses of PNU (7 and 70 µg/kg equating to 26 and 260 nmoles/kg), initially assuming that 5% of the agonist would penetrate the brain.…”

Synaptic Soluble and Membrane-Bound Choline Acetyltransferase as a Marker of Cholinergic Function In Vitro and In Vivo

“…It is necessary to understand the true mechanisms of the regulation, maintenance and recovery of brain functions. It should be noted that studies on synaptic fraction levels were carried out along these lines from the beginning [4,18,[21][22][23][24][25][26][27][28][29][30][31].…”

“…cChAT activation was observed under acute ischemia or hypoxia at all intensities [27,29,141]. mChAT or both mChAT and cChAT activation was revealed under acute and chronic ischemia and only in severe hypoxia (4.5% O 2 ) [27][28][29]141]. When the activation of ChAT was observed (165-170%), extracellular mAChE (the predominant isoform of mAChE) was simultaneously activated [141].…”

“…The inhibitory reactions of ChAT under ischemic/hypoxic conditions were revealed as well. It was found that these conditions decrease cChAT or mChAT or both cChAT and mChAT activity [27][28][29]141]. Also, a negative correlation has been found between cChAT activity and the c-protein content and a positive correlation has been found between mChAT activity and the m-protein content [27,29,141].…”

Improved spatial learning and memory performance following Tualang honey treatment during cerebral hypoperfusion-induced neurodegeneration

“…Chronic cerebral hypoperfusion induced by permanent bilateral occlusion of the common carotid arteries (2VO) in rats has been reported to be an effective model of neurodegenerative disorders especially Alzheimer's disease (AD) [1,19]. 2VO induced chronic cerebral hypoperfusion enhances the formation of Reactive Oxygen Species in the brain [20].…”