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Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline

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Abstract

Astrocytes are most abundant glial cell type in the brain and play a main defensive role in central nervous system against glutamate-induced toxicity by virtue of numerous transporters residing in their membranes and an astrocyte-specific enzyme glutamine synthetase (GS). In view of that, a dysregulation in the astrocytic activity following an insult may result in glutamate-mediated toxicity accompanied with astrocyte and microglial activation. The present study suggests that the lipopolysaccharide (LPS)-induced inflammation results in significant astrocytic apoptosis compared to other cell types in hippocampus and minocycline could not efficiently restrict the glutamate-mediated toxicity and apoptosis of astrocytes. Upon LPS exposure 76 % astrocytes undergo degeneration followed by 44 % oligodendrocytes, 26 % neurons and 10 % microglia. The pronounced astrocytic apoptosis resulted from the LPS-induced glutamate excitotoxicity leading to their hyperactivation as evident from their hypertrophied morphology, glutamate transporter 1 upregulation and downregulation of GS. Therapeutic minocycline treatment to LPS-infused rats efficiently restricted the inflammatory response and degeneration of other cell types but could not significantly combat with the apoptosis of astrocytes. Our study demonstrates a novel finding on cellular degeneration in the hippocampus revealing more of astrocytic death and suggests a more careful consideration on the protective efficacy of minocycline.

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Acknowledgments

We thankfully acknowledge the Department of Biotechnology, Ministry of Science and Technology, Govt. of India, New Delhi for providing the financial support. Facilities developed through the DBT-Human Resource Development and Bioinformatics Infrastructural Facility Programmes from Department of Biotechnology have also been used in this study.

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

    Arpita Sharma, Nisha Patro & Ishan K. Patro

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  1. Arpita Sharma
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Correspondence to Ishan K. Patro.

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Sharma, A., Patro, N. & Patro, I.K. Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline. Cell Mol Neurobiol 36, 577–592 (2016). https://doi.org/10.1007/s10571-015-0238-y

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