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

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

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of the key contributors to motor deficits <strong>and</strong> cellular stress associated with<br />

hypoglycemia in diabetes which is suggested to cause more damage at molecular<br />

level than hyperglycemia. Dysfunction of cerebellar cholinergic receptors are<br />

reported in hypoglycemia <strong>and</strong> hyperglycemia (Antony et al., 2010).<br />

Brain stem<br />

Brain stem reticular formation has been considered to play an important<br />

role in generating behavioural states as well as in the modulation of pain sensation<br />

(Pare & Steriade 1993). These reticular functions originate from interacting<br />

neuronal groups in the brain stem, including cholinergic, adrenergic <strong>and</strong><br />

serotoninergic neurons (Steriade, 1996). Hypoglycemia result primarily from a<br />

lowered glucose level in the brain <strong>and</strong> it adversely affects the central <strong>and</strong><br />

autonomic nervous systems (Charles et al., 2005). When glucose level was<br />

lowered to 2.8 mmoles/L, the brain function was impaired in nondiabetic rats.<br />

Symptoms of hypoglycemia result from the actions of hormones <strong>and</strong><br />

neurotransmitters in the process of restoring blood glucose levels. Severe<br />

hypoglycemia triggers a cascade of events in vulnerable neurons that culminate in<br />

cell death even after glucose normalization (Suh et al. 2003; 2005). Brainstem is<br />

an important part of the brain in monitoring the glucose status <strong>and</strong> the regulation<br />

of feeding (Guillod et al., 2003). Also, it serves as one of the key centres of the<br />

central nervous system for regulating body homeostasis. Present study on<br />

brainstem muscarinic receptors showed that the total muscarinic receptors<br />

increased during hypoglycemic condition compared to diabetic <strong>and</strong> control.<br />

<strong>Muscarinic</strong> <strong>M1</strong> receptors are decreased <strong>and</strong> muscarinic <strong>M3</strong> receptors are increased<br />

during hypoglycemia. RT-PCR analysis also revealed a down regulation of the<br />

muscarinic <strong>M1</strong> receptor mRNA level during glucose deprivation in hypoglycemia.<br />

This is in accordance with our receptor binding studies. Also, confocal studies<br />

using specific antibodies of muscarinic <strong>M1</strong> <strong>and</strong> <strong>M3</strong> in brain stem confirmed the<br />

Real time PCR analysis <strong>and</strong> binding assays. The adverse effects of mild<br />

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