Microglia are the major type of glial cells in the central nervous system and crucial in inflammatory response such as the release of pro-inflammatory cytokines. Several studies showed that inflammations are involved in cognitive disorders including Alzheimer's disease. However, the underlying mechanisms are unclear. Hence, we investigated whether epigenetic modifications are involved in the inflammations-evoked cognitive impairments.
Male ddY-mice (6 weeks) were intraperitoneally injected with lipopolysaccharide (LPS). Twenty-four hours after LPS injection, the cognitive function was determined by novelty objective recognition test. Pretreatment with a non-selective histone deacetylase (HDAC) inhibitor suberoyl anilide hydroxamic acid (SAHA, Vorinostat) was injected 1 hour before LPS injection.
The LPS treated-mice were showed the cognitive impairment and microglia activation in the hippocampus. Pretreatment with SAHA suppressed LPS-evoked cognitive impairment.
These data suggest that inflammation-induced cognitive disfunction were evoked by epigenetic modification such as the acetylation of histone. Furthermore, HDAC inhibitors could be the potential drug target for cognitive disorders.

To: 要旨(抄録)