title: Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation.
abstract: Chronic systemic inflammation induces age-dependent differential phenotypic changes in microglia and astrocytes, yielding an anti-inflammatory cell phenotype in young rats and a proinflammatory cell phenotype in middle-aged rats. These observations prompted further investigation of the functional outcomes of the resultant differential microglial phenotypic changes. The present study examined the effects of age-dependent differential microglial phenotypic changes following chronic systemic inflammation on the formation of the post-tetanic potentiation (PTP) and long-term potentiation (LTP) in the hippocampus. Microglia formed a proinflammatory cell phenotype to express ED1 and interleukin-1β (IL-1β) in the hippocampal CA1 region of middle-aged rats, but not in young rats following the establishment of adjuvant arthritis (AA). Furthermore, AA induced deficits in the formation of LTP in the Schaffer collateral-CA1 synapses of middle-aged rats, but not in young rats. On the other hand, the formation of PTP was impaired in both young and middle-aged AA rats. Minocycline, a known inhibitor of microglial activation, was systemically administered to middle-aged AA rats significantly restoring the mean magnitudes of both PTP and LTP. The mean expression levels of ED1 and IL-1β were significantly suppressed. These observations strongly suggest that chronic systemic inflammation induces deficits in the hippocampal LTP in middle-aged rats through neuroinflammation mainly induced by microglia.
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000375:Aging; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced; D001253:Astrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D017628:Microglia / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013569:Synapses / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D053583:Interleukin-1beta; D008911:Minocycline