Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

causes reduced cerebral energy metabolism leading to cognitive dysfunction by
inhibiting the synthesis of adenosine triphosphate (ATP) and acetyl CoA which
results in cholinergic deficiency supported by reduced ChAT activity in
hippocampus (Prickaerts et al., 1999) and increased AChE activity in rat brain
(Sonkusare et al., 2005). The enhancement of cholinergic activity by inhibition of
AChE enzyme is the main stay of symptomatic treatment of dementia (Siddiqui &
Levey, 1999).
Cholinergic neurons are widely distributed in the central nervous
system.They have effects on postsynaptic neurons and induce long-term
potentiation of synaptic transmission (LTP) and long term memory through a
series of signal transduction mechanisms. The dysfunction or loss of cholinergic
neuron is closely correlated with the decreasing ability of learning and memory
formation. The reduction of ChAT is correlated with the severity of dementia and
pathologic changes (Rodrigo et al., 2004). The altered expression of cholinergic
enzymes, AChE and ChAT possibly relate to the reported delayed nerve
transmission and impaired brain functions (Bartus et al., 1982).
Cognitive decline in AD brain seems to be related to impaired cholinergic
transmission that involves the synthesis of ACh by ChAT, release of ACh, binding
to postsynaptic receptors and rapid withdrawal of ACh by cholinesterases
(Ferna´ndez-Go´mez et al., 2009). Reduced activities of choline acetyl-transferase
(Coyle et al., 1983; DeKosky et al., 2002) and acetylcholinesterase from
cholinergic and non-cholinergic neurons (Kuhl et al., 1999; Blusztajn & Berse,
2000; Shinotoh et al., 2000) are associated with cognitive decline in
neurodegenerative diseases. The altered AChE and ChAT expression causes
specific alteration in ACh levels and mAChRs, leading to cholinergic dysfunction
on diabetes which is exacerbated by its complication, hypoglycemia. Present study
showed central cholinergic deficit associated with cognitive impairment during
hypoglycemia in diabetes.
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