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

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

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114<br />

Discussion<br />

shows impaired expression thereby function, during hypoglycemia which<br />

contributes to hypoglycemia associated functional deficit.<br />

Hippocampus<br />

The hippocampus is highly enriched in cholinergic terminals which<br />

originate from the medial septal pathways, <strong>and</strong> this system has a profound effect<br />

on hippocampal neuron functionality <strong>and</strong> reports demonstrated that the most<br />

abundant muscarinic receptor in the hippocampus is that of the musacrinic <strong>M1</strong><br />

subtype (Krnjevic, 1993; Levey, 1995). Excitatory modulations by muscarinic<br />

cholinergic receptors in hippocampal neurons have been well recognized. The<br />

high density of the muscarinic <strong>M1</strong> receptor protein in this region of the CA1<br />

subfield (Levey, 1995) supports the likely involvement of this subtype as a<br />

participant in the cholinergic modulation of protein synthesis <strong>and</strong> excitatory<br />

neuronal modulations. Diabetes mellitus <strong>and</strong> its most common treatment side<br />

effect, hypoglycemia, have multiple effects on the central nervous system.<br />

Prolonged or profound hypoglycemia leads to coma, seizures <strong>and</strong> potentially<br />

permanent brain damage (McCall, 2004).<br />

Because of the numerous modulatory effects exerted through<br />

phosphoinositide- linked muscarinic receptors in the hippocampus, we evaluated<br />

how the muscarinic receptors respond to hypoglycemic stress. Significant<br />

alterations in binding parameters <strong>and</strong> gene expression in total muscarinic,<br />

muscarinic <strong>M1</strong>, <strong>M3</strong> receptors were observed following hypoglycemia in diabetic<br />

<strong>and</strong> control rats. We observed a transient decreases in the mRNA levels of<br />

muscarinic receptor subtypes following recurrent episode of hypoglycemia.<br />

Immunohistochemistry study of muscarinic <strong>M1</strong>, <strong>M3</strong> receptors in the hippocampus<br />

of control <strong>and</strong> experimental rats using confocal microscope confirmed a similar<br />

expression pattern which confirmed at protein level. Neurons react to the decrease<br />

in oxygen <strong>and</strong> glucose by initiating a series of adaptive responses to mitigate<br />

excitotoxicity. Both long term mechanisms involving alterations in gene

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