The age-related attenuation in long-term potentiation is associated with microglial activation.

Abstract:

:It is well established that inflammatory changes contribute to brain ageing, and an increased concentration of proinflammatory cytokine, interleukin-1beta (IL-1beta), 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-1alpha, IL-18 and interferon-gamma (IFNgamma), 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.

journal_name

J Neurochem

authors

Griffin R,Nally R,Nolan Y,McCartney Y,Linden J,Lynch MA

doi

10.1111/j.1471-4159.2006.04165.x

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

1263-72

issue

4

eissn

0022-3042

issn

1471-4159

pii

JNC4165

journal_volume

99

pub_type

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