Abstract
Hypoglycemia is the major problem to blood glucose homeostasis in treatment of diabetes and is associated with severe irreversible consequences including seizures, coma and death. GABAergic inhibitory function in the cerebral cortex plays an important role in controlling the excitability and responsiveness of cortical neurons. Present study analysed effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cortical GABA receptor binding, GABAAά1, GABAB receptor subtype expression, GAD and GLUT3 expression. Diabetic rats showed decreased [3H] GABA binding in the cerebral cortex compared to control while hypoglycemia exacerbated the decrease. GABA receptor subunits; GABAAά1, GABAB and GAD expression significantly decreased in diabetic rats whereas hypoglycemia significanly decreased the expression compared to diabetic. GLUT3 expression significantly up regulated during both hypo and hyperglycemia. Our results showed that hypoglycemia and hyperglycemia decreased GABAergic neuroprotective function in the cerebral cortex, which account for the increased vulnerability of cerebral cortex to subsequent neuronal damage during hypo/hyperglycemia.
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Abbreviations
- GABA:
-
Gamma-aminobutyric acid
- GAD:
-
Glutamate decarboxylase
- STZ:
-
Streptozotocin
References
Bhardwaj SK, Sandhu SK, Sharma P, Kaur G (1999) Impact of diabetes on CNS: role of signal transduction cascade. Brain Res Bull 49:155–162
Tkacs N, Pan Y, Raghupathi R, Dunn-Meynell A, Levin B (2005) Cortical Fluoro-Jade staining and blunted adrenomedullary response to hypoglycemia after noncoma hypoglycemia in rats. Cereb Blood Flow Metabol 25:1645–1655
Tomlinson DR, Gardiner NJ (2008) Glucose neurotoxicity. Nat Rev Neurosci 9:36–45
Lipton SA, Nicotera P (1998) Calcium, free radicals and excitotoxins in neuronal apoptosis. Cell Calcium 23:165–171
Duchen MR (2000) Mitochondria and calcium: from cell signalling to cell death. J Physiol 529:57–68
Abdelmalik PA, Shannon P, Yiu A, Liang P, Adamchik Y, Weisspapir M, Samoilova M, McIntyre BW, Carlen PL (2007) Hypoglycemic seizures during transient hypoglycemia exacerbate hippocampal dysfunction. Neurobiol Dis 26:646–660
Joseph A, Antony S, Paulose CS (2008) Increased glutamate receptor gene expression in the cerebral cortex of insulin induced hypoglycemic and streptozotocin-induced diabetic rats. Neurosci 156:298–304
Joseph Anu, Peeyush Kumar T, Nandhu MS, Paulose CS (2010) Enhanced NMDAR1, NMDA2B and mGluR5 receptors gene expression in the cerebellum of insulin induced hypoglycaemic and streptozotocin induced diabetic rats. Eur J Pharmacol 630:61–68
Gregory C, Mathews MD (2007) The dual roles of GABA in seizures and epilepsy generate more excitement. Epilepsy Curr 7:28–30
Labrakakis C, Müller T, Schmidt K, Kettenmann H (1997) GABA(A) receptor activation triggers a Cl − conductance increase and a K + channel blockade in cerebellar granule cells. Neuroscience 79:177–189
Walker MC, Ruiz A, Kullmann DM (2002) Do mossy fibers release GABA? Epilepsia 5:196–202
Arison RN, Ciaccio EI, Glitzer MS, Cassaro JA, Pruss MP (1967) Light and electron microscopy of lesions in rats rendered diabetic with Streptozotocin. Diabetes 16:51–56
Hohenegger M, Rudas B (1971) Kidney function in experimental diabetic ketosis. Diabetologia 7:334–338
Flanagan DE, Evans ML, Monsod TP, Rife F et al (2003) The influence of insulin on circulating ghrelin. Am J Physiol Endocrinol Metab 284:E313–E316
Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. The disposition of [3H] norepinephrine, [3H] dopamine and [3H] dopa in various regions of the brain. J Neurochem 13:655–669
Kurioka S, Toshiaki k, Makoto M (1981) Effect of sodium and bicarbonate ions on GABA receptor binding in synaptic membrane of rat brain. J Neurochem 37:418–421
Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672
Lowry OH, Roserbbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275
Suh SW, Aoyama K, Matsumori Y, Liu J, Swanson RA (2005) Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment. Diabetes 54:1452–1458
Hoyer S (2002) The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update. J Neural Transm 109:341–360
Messier C, Gagnon M (1996) Glucose regulation and cognitive functions: relation to Alzheimer’s disease and diabetes. Behav Brain Res 75:1–11
Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gispen WH (1994) Cerebral function in diabetes mellitus. Diabetologia 37:643–650
Macdonald RL (2001) GABAA receptor defects can cause epilepsy. Epilepsy Curr 2:74
Kaila K (1994) Ionic basis of GABAA receptor channel function in the nervous system. Prog Neurobiol 42:489–537
Narita K, Nishihara M, Takahashi M (1994) Concomitant regulation of running activity and metabolic change by the ventromedial nucleus of the hypothalamus. Brain Res 642:290–296
Nonogaki K, Iguchi A, Sakamoto N (1994) Bicuculline methiodide influences the central nervous system to produce hyperglycemia in rats. J Neuroendocrinol 6:443–446
Schulz DW, Macdonald RL (1981) Barbiturate enhancement of GABA-mediated inhibition and activation of chloride ion conductance: correlation with anticonvulsant and anesthetic actions. Brain Res 209:177–188
Ryan CM, Williams TM (1993) Effects of insulin-dependent diabetes on learning and memory efficiency in adults. J Clin Exp Neuropsychol 15:685–700
Vannucci RC, Vannucci SJ (1978) Cerebral carbohydrate metabolism during hypoglycemia and anoxia in newborn rats. Ann Neurol 4:73–79
Maher F, Vannucci SJ, Simpson IA (1993) Glucose transporter isoforms in brain: absence of GLUT3 from the blood-brain barrier. J Cereb Blood Flow Metab 13:342–345
McCall AL (1992) The impact of diabetes on the CNS. Diabetes 41:557–570
Acknowledgments
This work was supported by research grants from DBT, DST, ICMR, Govt. of India and KSCSTE, Govt. of Kerala to Dr. C. S. Paulose. Sherin Antony thanks CSIR for SRF. Peeyush Kumar T thanks DST for SRF.
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Antony, S., Peeyush Kumar, T., Kuruvilla, K.P. et al. Decreased GABA Receptor Binding in the Cerebral Cortex of Insulin Induced Hypoglycemic and Streptozotocin Induced Diabetic Rats. Neurochem Res 35, 1516–1521 (2010). https://doi.org/10.1007/s11064-010-0210-7
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DOI: https://doi.org/10.1007/s11064-010-0210-7