Diabetes Mellitus is associated with increased risk of cognitive and behavioural disorders with hitherto undeciphered role of glia. Glia as majority population in brain serve several vital functions, thus require pertinent revelation to further explicate the mechanisms affecting the brain function following diabetes. In this study we have evaluated glial changes in terms of phenotypic switching, proliferation and expression of activation cell surface markers and associated cellular degeneration in hippocampus following STZ-induced diabetes and caused cognitive impairments. Experimental diabetes was induced in Wistar rats by a single dose of STZ (45 mg/kg body weight; intraperitoneally) and changes were studied in 2nd, 4th and 6th week post diabetes confirmation using Barnes maze and T-maze test, immunohistochemistry and image analysis. An increase in GFAP expression sequentially from 2nd to 6th weeks of diabetes was analogous with the phenotypic changes and increased astrocyte number. Elevated level of S100β with defined stellate morphology further confirmed the astrocytosis following diabetes. Enhanced level of Iba-1 and MHC-II revealed the corroborated microglial activation and proliferation following diabetes, which was unresolved till date. Increased caspase-3 activity induced profound cell death upto 6th weeks post diabetes confirmation. Such caspase 3 mediated cellular damage with a concomitant activation of the astrocytes and microglia suggests that diabetes linked cell death activates the astrocytes and microglia in hippocampus which further underpin the progression and severity of brain disorders resulting in cognitive and behavioural impairments.
Behavioral impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/kg body weight; intraperitoneally). Motor function alterations were studied using Rotarod test (motor coordination) and grip strength (muscle activity) at 2nd, 4th, 6th, 8th, 10th, and 12th week post-diabetic confirmation. Scenario of glial (astroglia and microglia) activation, cell death and glutamate transportation was gaged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labeling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioral alterations following STZ-induced diabetes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.