Cholinergic adaptations

Figure 6.4 Microdialysis perfusion of histamine into the cholinergic zone of the basal forebrain increases wakefulness in a dose-dependent fashion. The animals spent almost half of their time in wakefulness during the 2 h period of perfusion of the highest dose (1,000 p,M). In contrast, approximately 12% of the time was spent in wakefulness during the 2 h perfusion period of artificial CSF (i.e. the control day). Adapted from Ramesh et al. (2004).

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Because it is possible that free acetylcholine may constitute the predominant fraction of the reduced total which is observed after adaptation has occurred, our experiments do not rule out the possibility that cholinergic receptors may acquire tolerance to acetylcholine, as Brodeur and DuBois suggest. We are not prepared to evaluate the importance of increased resistance to carbachol which they present in support of their hypothesis, in view of the strong nicotinic component of the action of that drug. 

Re-adaptation of cholinergic receptors after prolonged blockade may contribute to withdrawal effects of paroxetine... 

Karezmar, A.G. and Richardson, D.L., 1982, Cholinergic mechanisms, schizophrenia and neuropsychlatrie adaptive dysfunctions In Cholinergic mechanisms and adaptive dysfunctions ed. by M.M. Singh, D.M. Warburton, and H Lai. Plenum Press, New York. 

Weeker, L.. Mobley, P. L.. and Dettbam, W.-D, (1977). Central cholinergic mechanisms underlying adaptation to reduced cholinesterase activity. Riochem. Phartnacol. 26,633-637. 

It appeared that cholinergic transmission performed other new functions. It can modulate various aspects of immune function, both innate and adaptive. Cholinergic transmission influences immune cell proliferation, cytokine production, differentiation of T-helper cells, and antigen presentation. These effects are mediated by cholinergic mAChR and nAQiR and other cholinergic components present in immune cells, for example, a7 nAQiR has the ability to induce anti-inflammatory activity [89]. This is probably one of the reasons why acetylcholinesterase inhibitors (AChEIs) act far broader than just to the inhibition of AChE. 

Fig. 5 Schematic of stem cell therapy in AD. Neurodegeneration in AD is characterized by loss of cholinergic neurons in the presence of senile plaques and neurofibrillary tangles. Regenerative strategies for AD treatment include the injection of stem cell-derived cholinergic neurons to replace degenerated cells. Stem cells can also be delivered to the basal forebrain to provide trophic support via the release of growth factors. Alternatives include the administration of antibodies to sequester pathological hallmarks and promote endogenous neurogenesis. Adapted from [132].

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