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

More documents

Recommendations

Info

motor control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebral motor cortex and the spinocerebellar tract (Roberta & Peter, 2003). Abundance of GABA receptors in the cerebellar cortex confirms the importance of GABAergic inhibitory action in signal processing and homeostasis. Results of our study on cerebellar GAD and GABA receptors showed decreased Bmax and decreased expression of GAD in hypoglycemic rats compared to diabetic and control which put forward decreased GABAergic functional regulation in the cerebellum. There is currently enough anatomical, physiological and theoretical evidence to support the hypothesis that cerebellum is the region of the brain for learning, basal ganglia for reinforcement learning and cerebral cortex for unsupervised learning (Doya, 1999). GABAAα1 and GABAB receptor gene expression showed a significant downregulation in hypoglycemic rats. GABAAα1 subunit is considered to be an essential subunit for inhibitory synaptic transmission in the matured cerebellar cortex (Takayama & Inoue, 2004) and the decreased GABA receptor subunit contributes to blockade of inhibitory synaptic transmission which contributes to seizure initiation during recurrent hypoglycemia. GABAB receptors play a major role in inhibitory neurotransmission in the mammalian brain (Bowery, 2006) and are intimately involved in synaptic plasticity (Davies et al., 1991), nociception (Gordon et al., 1995) and some neuronal disease states. The changes in GABAA receptor subunit contribute to the changes in inhibitory function that underlie occurrence of recurrent seizures (Jean-Marc, 2008). Presynaptically, GABAB receptors inhibit the release of GABA, via autoreceptors, and excitatory neurotransmitters (Perkington & Sihra, 1998). Postsynaptic GABAB receptor activation elicits increased outward potassium current, causing hyperpolarisation. This gives rise to the slow late component of the inhibitory postsynaptic potential (IPSP) important in signal processing (Misgeld et al., 1995). Postsynaptic GABA receptors also 125
126 Discussion modulate the second messenger responses to other neurotransmitters such as noradrenaline and 5-hydroxytryptamine (Karbon et al.,, 1984). The cellular basis of motor learning has been mostly attributed to long term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole-cell patchclamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting rebound potentiation (RP) of GABAA receptor mediated inhibitory postsynaptic currents (IPSCs) (Bibiana et al., 2008; Peer et al., 2009). Purkinje cells express a high density of GABAB receptor, a Gi/o-protein-coupled receptor for the inhibitory neurotransmitter GABA (Kuner et al., 1999). As the entire output of the cerebellar cortex is carried by the firing of Purkinje cells, any mechanism able to modulate the firing pattern of Purkinje cells will influence cerebellar function. Purkinje cells fire spontaneously, even in the absence of glutamate input and the pattern of firing is very strongly influenced by high conductance, high frequency GABAergic inputs (Hausser & Clark, 1997). Considering the importance of GABA transmission in influencing Purkinje cell firing (Kanjhan et al., 1999), decreased GABA receptor expression in cerebellum is suggested to affect GABAergic transmission. Immunohistochemical studies using specific antibodies of GABAAα1 have proved the decreased expression status of this receptor subtype in the cerebellum. In the present study, behavioural study using grid walk test showed impaired motor performance in hypoglycemic rats. Reduction in spontaneous motor activity follows recurrent hypoglycemia is reported by Duncan et al (2010). Loss of coordination of motor movement, inability to judge distance and timing, incapacity to perform rapid alternating movements, and hypotonia have been reported during cerebellar damage (Blumer et al., 2004) and hypoglycemic induced cerebellar dysfunction . These studies indicate that during hypoglycemic stress, the subunits of GABA receptors assemble in different combinations with
Page 2:
MUSCARINIC M1, M3, NICOTINIC, GABAA
Page 5 and 6:
ACKNOWLEDGEMENT To the Almighty God
Page 7 and 8:
Seema Chandran, Ms. Neema Ani Manga
Page 9 and 10:
ABBREVIATIONS 5-HIAA 5 Hydroxy indo
Page 11 and 12:
PFC Prefrontal cortex PLC Phospholi
Page 13 and 14:
GABAC Receptors 34 Glutamic Acid De
Page 15 and 16:
Behavioural response of control and
Page 17 and 18:
the cerebral cortex of control and
Page 19 and 20:
Muscarinic M1 receptor analysis Sca
Page 21 and 22:
REAL TIME-PCR ANALYSIS 81 Real Time
Page 23 and 24:
Real Time PCR analysis of GABAAα1
Page 25 and 26:
pancreas of control and experimenta
Page 27 and 28:
utilization is decreased in the bra
Page 29 and 30:
impairment, coma or seizure (Cryer,
Page 31 and 32:
achieving optimal blood sugar contr
Page 33 and 34:
OBJECTIVES OF THE PRESENT STUDY 1.
Page 35 and 36:
Literature Review Diabetes mellitus
Page 37 and 38:
12 Literature Review from the adren
Page 39 and 40:
14 Literature Review Hypoglycemic c
Page 41 and 42:
16 Literature Review respectively)
Page 43 and 44:
18 Literature Review in extracellul
Page 45 and 46:
20 Literature Review substrates in
Page 47 and 48:
22 Literature Review nucleus, altho
Page 49 and 50:
24 Literature Review al., 1990; Lev
Page 51 and 52:
26 Literature Review muscarinic M2
Page 53 and 54:
Signal transduction by muscarinic a
Page 55 and 56:
30 Literature Review nicotinic acet
Page 57 and 58:
GABAA Receptors 32 Literature Revie
Page 59 and 60:
34 Literature Review GABAB-mediated
Page 61 and 62:
36 Literature Review (Erlander et a
Page 63 and 64:
38 Literature Review which could be
Page 65 and 66:
40 Literature Review administration
Page 67 and 68:
42 Literature Review the hippocampu
Page 69 and 70:
44 Literature Review understanding
Page 71 and 72:
Confocal Dyes Rat primary antibody
Page 73 and 74:
antipyryl)-p-benzo quinoneimine. Th
Page 75 and 76:
was analyzed. Data was expressed as
Page 77 and 78:
ANALYSIS OF THE RECEPTOR BINDING DA
Page 79 and 80:
Taqman probes of muscarinic M1, M3,
Page 81 and 82:
Taylor, 1968). The islets were isol
Page 83 and 84:
Results BODY WEIGHT AND BLOOD GLUCO
Page 85 and 86:
60 Results IIH and C + IIH rats sho
Page 87 and 88:
Real Time-PCR analysis of muscarini
Page 89 and 90:
Real Time PCR analysis of SOD 64 Re
Page 91 and 92:
66 Results GABAAα1 receptor antibo
Page 93 and 94:
68 Results compared to diabetic gro
Page 95 and 96:
70 Results compared to diabetic rat
Page 97 and 98:
72 Results Muscarinic M3 receptor a
Page 99 and 100: Muscarinic M3 receptor analysis 74
Page 101 and 102: 76 Results group, α7 nAChR mRNA si
Page 103 and 104: 78 Results diabetic rats. In C + II
Page 105 and 106: Muscarinic M1 receptor analysis 80
Page 107 and 108: Real Time-PCR analysis of α7 nAChR
Page 109 and 110: Real Time PCR analysis of phospholi
Page 111 and 112: HIPPOCAMPUS Total muscarinic recept
Page 113 and 114: 88 Results IIH and C + IIH group sh
Page 115 and 116: 90 Results group, GLUT3 mRNA signif
Page 117 and 118: 92 Results α7 nACh receptor antibo
Page 119 and 120: GABA receptor analysis 94 Results S
Page 121 and 122: 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: 124 Discussion al., 1988). Low bloo
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 and 174: 148 Summary specific antibodies con
Page 175 and 176: 150 Summary 16. Transcription facto
Page 177 and 178: References Abdelmalik PA, Shannon P
Page 179 and 180: Akwa Y, Ladurelle N, Covey F, Bauli
Page 181 and 182: Arison RN, Ciaccio EI, Glitzer MS,
Page 183 and 184: Balters E, Francesco M. (2002). New
Page 185 and 186: Bettler B, Kaupmann K, Mosbacher J,
Page 187 and 188: Boess FG, De Vry J, Erb C, Flessner
Page 189 and 190: Brezenoff HE, Xiao YF. (1986). Acet
Page 191 and 192: Caulfield MP, Birdsall NJM. (1998).
Page 193 and 194: Cherubini E, Martina M, Sciancalepo
Page 195 and 196: Cryer PE. (2002b). The pathophysiol
Page 197 and 198: Delgado Esteban M, Almeida A, Bolan
Page 199 and 200: Dutar P, Nicoll RA. (1989). Pharmac
Page 201 and 202:
Exton JH, Jefferson LS, Butcher RW,
Page 203 and 204:
Frier B. (2000). Hypoglycaemia—cl
Page 205 and 206:
Gerich JE, Schneider V, Dippe SE, L
Page 207 and 208:
Golding DW, Pow DV. (1990). Neurose
Page 209 and 210:
Haddad GG, Jiang C. (1993). Mechani
Page 211 and 212:
Havel PnJ, Dunning BnE, Verchere Cn
Page 213 and 214:
Hsu KS, Huang CC, Gean PW. (1995).
Page 215 and 216:
Johnson E, Deckwerth T. (1993). Mol
Page 217 and 218:
Kanjhan R, Housley GD, Burton LD, C
Page 219 and 220:
Kelley GG, Zawalich KC, Zawalich WS
Page 221 and 222:
Krnjevic K. (1993). Central choline
Page 223 and 224:
Lackovic Z, Salkovic M, Kuci Z, Rel
Page 225 and 226:
Lipton P. (1999). Ischemic cell dea
Page 227 and 228:
Mares P, Kubova H, Zouhar A, Folber
Page 229 and 230:
McCulloch DK, Raghu PK, Koerker DJ,
Page 231 and 232:
Miyakawa T, Yamada M, Duttaroy A, W
Page 233 and 234:
Nusser Z, Sieghart W, Somogyi P. (1
Page 235 and 236:
Paramo B, Hernández-Fonseca K, Est
Page 237 and 238:
Peeyush KT, Savitha B, Sherin A, An
Page 239 and 240:
Quan L, Meili G, Chang BS, Lowenste
Page 241 and 242:
Robinson R, Krishnakumar A, Paulose
Page 243 and 244:
Salkovic M, Lackovic Z. (1992). Bra
Page 245 and 246:
Scheucher A. Alvarez AL, Torres N,
Page 247 and 248:
(2002). Sulfonylurea receptor type
Page 249 and 250:
Steriade M. (1996). Arousal: revisi
Page 251 and 252:
Takayama C, Inoue Y. (2003). Normal
Page 253 and 254:
Unger J, McNeill TH, Moxley RT 3rd,
Page 255 and 256:
pentabromodiphenyl ether (PBDE 99).
Page 257 and 258:
Weiner DM, Levey AI, Brann MR. (199
Page 259 and 260:
Wredling R, Levander S, Adamson U,
Page 261 and 262:
Zhao W, Chen H, Xu H, Moore E, Meir
Page 263 and 264:
6. Anju T R, Pretty Mary Abraham, S
Page 265 and 266:
Body weight (gm) 300 250 200 150 10
Page 267 and 268:
Figure-3 Blood glucose levels at di
Page 269 and 270:
Figure-5 Behavioural response of co
Page 271 and 272:
Figure-7 Scatchard analysis of [ 3
Page 273 and 274:
Page 275 and 276:
Figure-11 Real Time PCR amplificati
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
C D + IIH Figure--25 Muscarinic M1
Page 291 and 292:
Figure--27 α 7 nACh receptor expre
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Figure--47 Muscarinic M1 receptor e
Page 313 and 314:
Figure--49 α7 nicotinic acetylchol
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Figure--71 α7 nicotinic acetylchol
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
Page 357 and 358:
C Figure--93 GABAAα1 receptor expr
Page 359 and 360:
Page 361 and 362:
Page 363 and 364:
Page 365 and 366:
Figure-101 Real Time PCR amplificat
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
Figure—113 Muscarinic M3 receptor
Page 379 and 380:
Figure--115 GABAAα1 receptor expre
Page 381 and 382:
Figure-117 Scatchard analysis of [
Page 383 and 384:
Figure-119 Scatchard analysis of [
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Figure-131 Muscarinic M1 receptor e
Page 397:
C D + IIH Figure-133 GABAAα1 recep
show all

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?