Genes Involved by Dexamethasone in Prevention of Long-Term Memory Impairment Caused by Lipopolysaccharide-Induced Neuroinflammation.

Inflammatory activation within the brain is linked to a decrease in cognitive abilities; however, the molecular mechanisms implicated in the development of inflammatory-related cognitive dysfunction and its prevention are poorly understood. This study compared the responses of hippocampal transcriptomes 3 months after the striatal infusion of lipopolysaccharide (LPS; 30 µg), resulting in memory loss, or with dexamethasone (DEX; 5 mg/kg intraperitoneal) pretreatment, which abolished the long-term LPS-induced memory impairment. After LPS treatment, a significant elevation in the expression of immunity/inflammatory-linked genes, including chemokines ( Cxcl13 ), cytokines ( Il1b and Tnfsf13b ), and major histocompatibility complex (MHC) class II members ( Cd74 , RT1-Ba , RT1-Bb , RT1-Da , and RT1-Db1 ) was observed. DEX pretreatment did not change the expression of these genes, but significantly affected the expression of genes encoding ion channels, primarily calcium and potassium channels, regulators of glutamate ( Slc1a2 , Grm5 , Grin2a ), and GABA ( Gabrr2 , Gabrb2 ) neurotransmission, which enriched in such GO biological processes as "Regulation of transmembrane transport", "Cognition", "Learning", "Neurogenesis", and "Nervous system development". Taken together, these data suggest that (1) pretreatment with DEX did not markedly affect LPS-induced prolonged inflammatory response; (2) DEX pretreatment can affect processes associated with glutamatergic signaling and nervous system development, possibly involved in the recovery of memory impairment induced by LPS.