title: Impact of indomethacin on neuroinflammation and hippocampal neurogenesis in aged mice.
abstract: Age-induced neuroinflammation could be a contributing factor to the restricted neurogenesis in aged mice. Indomethacin, a common non-steroidal anti-inflammatory drug, has been demonstrated to partially restore neurogenesis under pathophysiological inflammation-associated conditions in adult C57BL/6 mice. This study investigated whether indomethacin is able to decrease age-related neuroinflammation in the hippocampus (24-month-old mice) and thereby stimulate neurogenesis. During hippocampal aging, the transcript expression of pro-inflammatory cytokines (Tnfα, Il-1α, Il-1β), the chemokine Mip-1α, and markers for activated astrocytes (Gfap, Lcn2, but not Vim and Serpina3n) and microglia (Iba1, F4/80, Cd68, Cd86) significantly increased. Treatment with indomethacin significantly decreased COX-1 and COX-2 transcript expression. Of the age-related inflammatory mediators, only Gfap and Iba1 were affected by indomethacin treatment in the hippocampus, with a significantly reduced transcript expression being detected for both markers. Neurogenesis was unaffected by indomethacin. Thus, our data reveal that administration of indomethacin to aged mice is not able to effectively decrease neuroinflammation and promote neurogenesis.
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Boehme
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany.
authors.forename: Madlen
authors.initials: M
authors.lastname: Guenther
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany; Institute of Anatomy II, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Stahr
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany; Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Liebmann
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Jaenisch
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany; Center for Sepsis Control and Care, University Hospital Jena, Jena, Germany.
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.affiliation: Hans-Berger Department of Neurology, University Hospital Jena, Friedrich-Schiller University, Jena, Germany. Electronic address: christiane.frahm@med.uni-jena.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Frahm
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016207:Cytokines; D008565:Membrane Proteins; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D007213:Indomethacin
keywords: Aging; Cytokines; Inflammation; Neurogenesis