title: Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline.
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.
authors.affiliation: School of Studies in Neuroscience, Jiwaji University, Gwalior, 474011, India.
authors.forename: Arpita
authors.initials: A
authors.lastname: Sharma
authors.affiliation: School of Studies in Neuroscience, Jiwaji University, Gwalior, 474011, India.
authors.forename: Nisha
authors.initials: N
authors.lastname: Patro
authors.affiliation: School of Studies in Neuroscience, Jiwaji University, Gwalior, 474011, India. ishanpatro@gmail.com.
authors.forename: Ishan K
authors.initials: IK
authors.lastname: Patro
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar
chemical_list: D027322:Amino Acid Transport System X-AG; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D053148:Caspase 3; D005974:Glutamate-Ammonia Ligase; D008911:Minocycline
keywords: Astrocytes; Glutamate transporter-1; Glutamine synthetase; Lipopolysaccharide (LPS); Minocycline