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

Abstract

Inflammatory activation within the brain was 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 responses of hippocampal transcriptomes 3 months after the striatal infusion of lipopolysaccharide, alone (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 alone, a significant elevation in the expression of immunity/inflammatory-linked genes, including chemokine (Cxcl13), cytokines (Il1b, Tnfsf13b), and major histocompatibility complex (MHC) class II members (Cd74, RT1-Ba, RT1-Bb, RT1-Da, RT1-Db1) was revealed. DEX pretreatment did not change expression of these genes, but significantly affected 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, the 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 by that in the recovery of memory impairment induced by LPS