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

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12. Insulin receptor mRNA level was studied in the brain regions and pancreas of experimental rats. A decreased expression of insulin receptor was observed in cerebral cortex whereas in cerebellum, brain stem, corpus striatum and hippocampus, there was an increased expression in hypoglycemic and diabetic rats. Pancreas of both hypoglycemic and diabetic rats showed decreased insulin receptor expression. 13. Antioxidant enzyme, SOD expression was studied in experimental rats. Results showed that in diabetic rats, its mRNA level was down regulated in cerebral cortex, cerebellum and hippocampus whereas in brain stem and corpus striatum, it was up regulated when compared to control. In D + IIH and C + IIH rats, SOD expression decreased in cerebral cortex, cerebellum, corpus striatum and hippocampus whereas brain stem showed increased expression. Pancreatic expression of SOD mRNA in hypoglycemic rats decreased significantly compared to diabetic and control. Oxidative stress seen in diabetic brain and pancreas were found to exacerbate by hypoglycemia. 14. Pro-apoptotic protein- Bax mRNA expression significantly up regulated in hypoglycemic brain regions - cerebral cortex, cerebellum, brain stem, corpus striatum, hippocampus and pancreas compared to diabetic and control. 15. Second messenger enzyme - phospholipase C showed a decreased expression in hypoglycemic and diabetic brain regions - cerebral cortex, cerebellum, brain stem, corpus striatum and hippocampus. In pancreas, there was a significant decrease in mRNA expression of phospholipase C in diabetic, D + IIH and C + IIH rats compared to control. 149
150 Summary 16. Transcription factor, CREB expression in the brain regions - cerebral cortex, cerebellum, brain stem and hippocampus showed decreased expression in hypoglycemic and diabetic rats. In corpus striatum, there was an increased CREB expression in diabetic rats compared to control whereas D + IIH and C + IIH rats showed decreased expression compared to diabetic. It is evident from our results that cholinergic, GABAergic receptor functional balance plays a major role in hypoglycemia and diabetes associated disorders. Gene expression studies along with immunohistochemistry showed a prominent functional disturbance in brain regions and pancreas of hypoglycemic and diabetic rats. These findings have important implications for understanding the molecular mechanisms underlying memory and cognitive impairment at second messenger and transcription level during recurrent hypoglycemia. Our studies showed hypoglycemic and hyperglycemic effect on brain functions by acetylcholine and GABA mediated through their receptor subtypes, second messenger enzymes and transcription factors. It is suggested that the corrective measures for the brain functional damage caused during diabetes and its treatment, through cholinergic and GABAergic receptors have therapeutic role in the management of diabetes and hypoglycemia - induced by anti-hyperglycemic treatment in diabetes.
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MUSCARINIC M1, M3, NICOTINIC, GABAA
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ACKNOWLEDGEMENT To the Almighty God
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Seema Chandran, Ms. Neema Ani Manga
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ABBREVIATIONS 5-HIAA 5 Hydroxy indo
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PFC Prefrontal cortex PLC Phospholi
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GABAC Receptors 34 Glutamic Acid De
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Behavioural response of control and
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the cerebral cortex of control and
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Muscarinic M1 receptor analysis Sca
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REAL TIME-PCR ANALYSIS 81 Real Time
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Real Time PCR analysis of GABAAα1
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pancreas of control and experimenta
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utilization is decreased in the bra
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impairment, coma or seizure (Cryer,
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achieving optimal blood sugar contr
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OBJECTIVES OF THE PRESENT STUDY 1.
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Literature Review Diabetes mellitus
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12 Literature Review from the adren
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14 Literature Review Hypoglycemic c
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16 Literature Review respectively)
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18 Literature Review in extracellul
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20 Literature Review substrates in
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22 Literature Review nucleus, altho
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24 Literature Review al., 1990; Lev
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26 Literature Review muscarinic M2
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Signal transduction by muscarinic a
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30 Literature Review nicotinic acet
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GABAA Receptors 32 Literature Revie
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34 Literature Review GABAB-mediated
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36 Literature Review (Erlander et a
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38 Literature Review which could be
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40 Literature Review administration
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42 Literature Review the hippocampu
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44 Literature Review understanding
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Confocal Dyes Rat primary antibody
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antipyryl)-p-benzo quinoneimine. Th
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was analyzed. Data was expressed as
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ANALYSIS OF THE RECEPTOR BINDING DA
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Taqman probes of muscarinic M1, M3,
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Taylor, 1968). The islets were isol
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Results BODY WEIGHT AND BLOOD GLUCO
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60 Results IIH and C + IIH rats sho
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Real Time-PCR analysis of muscarini
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Real Time PCR analysis of SOD 64 Re
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66 Results GABAAα1 receptor antibo
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68 Results compared to diabetic gro
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70 Results compared to diabetic rat
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72 Results Muscarinic M3 receptor a
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Muscarinic M3 receptor analysis 74
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76 Results group, α7 nAChR mRNA si
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78 Results diabetic rats. In C + II
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Muscarinic M1 receptor analysis 80
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Real Time-PCR analysis of α7 nAChR
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Real Time PCR analysis of phospholi
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HIPPOCAMPUS Total muscarinic recept
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88 Results IIH and C + IIH group sh
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90 Results group, GLUT3 mRNA signif
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92 Results α7 nACh receptor antibo
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GABA receptor analysis 94 Results S
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96 Results control. D + IIH and C +
Page 123 and 124: Discussion Glucose is the principal
Page 125 and 126: 100 Discussion The ability to sense
Page 127 and 128: 102 Discussion The Y-maze test is a
Page 129 and 130: 104 Discussion CHOLINERGIC ENZYME A
Page 131 and 132: 106 Discussion Pancreas Insulin sec
Page 133 and 134: 108 Discussion 2003). Cholinergic m
Page 135 and 136: 110 Discussion brain for learning,
Page 137 and 138: 112 Discussion hypoglycemia on brai
Page 139 and 140: 114 Discussion shows impaired expre
Page 141 and 142: 116 Discussion glycemic control is
Page 143 and 144: 118 Discussion release (Ilcol et al
Page 145 and 146: 120 Discussion al., 1992), it has t
Page 147 and 148: 122 Discussion metabolic cycles are
Page 149 and 150: 124 Discussion al., 1988). Low bloo
Page 151 and 152: 126 Discussion modulate the second
Page 153 and 154: 128 Discussion between excitation a
Page 155 and 156: 130 Discussion hypoglycemic seizure
Page 157 and 158: 132 Discussion Insulin secretion fr
Page 159 and 160: 134 Discussion hyper and hypoglycem
Page 161 and 162: 136 Discussion receptors in glucose
Page 163 and 164: 138 Discussion exacerbated by recur
Page 165 and 166: 140 Discussion Haces et al., 2010).
Page 167 and 168: 142 Discussion hypoglycemic and dia
Page 169 and 170: 144 Discussion transcription factor
Page 171 and 172: Summary 1. Insulin induced hypoglyc
Page 173: 148 Summary specific antibodies con
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6. Anju T R, Pretty Mary Abraham, S
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Body weight (gm) 300 250 200 150 10
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Figure-3 Blood glucose levels at di
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Figure-5 Behavioural response of co
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Figure-7 Scatchard analysis of [ 3
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Figure-11 Real Time PCR amplificati
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C D + IIH Figure--25 Muscarinic M1
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Figure--27 α 7 nACh receptor expre
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Figure--47 Muscarinic M1 receptor e
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Figure--49 α7 nicotinic acetylchol
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Figure--71 α7 nicotinic acetylchol
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C Figure--93 GABAAα1 receptor expr
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Figure-101 Real Time PCR amplificat
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Figure—113 Muscarinic M3 receptor
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Figure--115 GABAAα1 receptor expre
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Figure-117 Scatchard analysis of [
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Figure-119 Scatchard analysis of [
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Figure-131 Muscarinic M1 receptor e
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C D + IIH Figure-133 GABAAα1 recep
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