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The age‐related attenuation in long‐term potentiation is associated with microglial activation
Author(s) -
Griffin Rebecca,
Nally Rachel,
Nolan Yvonne,
McCartney Yvonne,
Linden James,
Lynch Marina A.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04165.x
Subject(s) - long term potentiation , microglia , proinflammatory cytokine , neuroinflammation , hippocampal formation , hippocampus , minocycline , neuroscience , inflammation , medicine , endocrinology , chemistry , biology , biochemistry , receptor , antibiotics
It is well established that inflammatory changes contribute to brain ageing, and an increased concentration of proinflammatory cytokine, interleukin‐1β (IL‐1β), has been reported in the aged brain associated with a deficit in long‐term potentiation (LTP) in rat hippocampus. The precise age at which changes are initiated is unclear. In this study, we investigate parallel changes in markers of inflammation and LTP in 3‐, 9‐ and 15‐month‐old rats. We report evidence of increased hippocampal concentrations of the proinflammatory cytokines IL‐1α, IL‐18 and interferon‐γ (IFNγ), which are accompanied by deficits in LTP in the older rats. We also show an increase in expression of markers of microglial activation, CD86, CD40 and intercellular adhesion molecules (ICAM). Associated with these changes, we observed a significant impairment of hippocampal LTP in the same rats. The importance of microglial activation in the attenuation of long‐term potentiation (LTP) was demonstrated using an inhibitor of microglial activation, minocycline; partial restoration of LTP in 15‐month‐old rats was observed following administration of minocycline. We propose that signs of neuroinflammation are observed in middle age and that these changes, which are characterized by microglial activation, may be triggered by IL‐18.