Enhanced NMDAR1, NMDA2B and mGlu5 receptors gene expression in the cerebellum of insulin induced hypoglycaemic and streptozotocin induced diabetic rats.
Glucose homeostasis in humans is an important factor for the functioning of the nervous system. A decrease in glucose content below a minimal level or hypoglycemia is dangerous for cells of the central and peripheral nerve system. In the present study we showed the effects of insulin induced hypoglycaemia and streptozotocin induced diabetes on the cerebellar glutamate receptor subunits and glutamate transporter. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. We found an up regulation in NMDA receptor number and gene expression of N-methyl-d-aspartic acid (NMDA(R1)), NMDA(2B), metabotrophic glutamate 5 (mGlu(5)) glutamate receptor subunits in experimental rats. The glutamate content was shown to be increased with decreased glutamate aspartate transporter (GLAST) gene expressions indicating lower reuptake of glutamate. The enhanced gene expression of NMDA(R1), NMDA(2B), mGlu(5) glutamate receptors were confirmed by immunohistochemistry studies. At the second messenger level, the IP3 content and IP3 receptors were enhanced in the cerebellum of both hypoglycaemic and diabetic rats increased. The present study showed that the enhanced glutamate content activates NMDA receptors, increasing the inositol triphosphate (IP3) content which mediates Ca(2+) overload in cells causing cell damage and neurodegeneration. Our results also showed that the enhanced glutamate receptor activity were more prominent in hypoglycaemic group compared to diabetic group. Further the neurodegeneration by the up regulation of glutamate receptor activity causing motor dysfunction was demonstrated by the Rotarod test. Thus our results suggest that enhanced NMDA receptor mediated neurodegeneration affect the motor learning and memory ability of an individual.
Anu
Joseph
J
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India.
Peeyush Kumar
T
T
Nandhu
Mohan Sobhana
MS
Paulose
Cheramadathikudiyil Skaria
CS
D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D015870:Gene Expression; D007003:Hypoglycemia / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin
D007328:Insulin; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013311:Streptozocin; C121001:NR2B NMDA receptor