کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4338405 | 1614860 | 2012 | 10 صفحه PDF | دانلود رایگان |
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.
► Systemic inflammation induced impairment of synaptic plasticity in middle-aged rats.
► This impairment was significantly restored by inhibition of microglial activation.
► This impairment is caused by activated microglia following systemic inflammation.
► Therefore, systemic inflammation accelerates the brain aging in middle age.
Journal: Neuroscience - Volume 216, 2 August 2012, Pages 133–142