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Astrocytic and microglial response in experimentally induced diabetic rat brain

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Abstract

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.

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Acknowledgments

Financial support from the Indian Council of Medical Research, New Delhi is thankfully acknowledged. Aarti Nagayach is an Indian Council of Medical Research (ICMR) Senior Research Fellow. Facilities developed through the DBT-Human Resource Development and Bioinformatics Infrastructural Facility through Department of Biotechnology Grants used in this study are thankfully acknowledged.

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  1. School of Studies in Neuroscience, Jiwaji University, Gwalior, 474011, Madhya Pradesh, India

    Aarti Nagayach, Nisha Patro & Ishan Patro

  2. School of Studies in Zoology, Jiwaji University, Gwalior, 474011, Madhya Pradesh, India

    Ishan Patro

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  1. Aarti Nagayach
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  3. Ishan Patro
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Nagayach, A., Patro, N. & Patro, I. Astrocytic and microglial response in experimentally induced diabetic rat brain. Metab Brain Dis 29, 747–761 (2014). https://doi.org/10.1007/s11011-014-9562-z

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