Changes in Behavior and the Expression of Ionotropic Glutamate Receptor Genes in the Brains of Adult Rats after Neonatal Administration of Bacterial Lipopolysaccharide

Many studies have shown that early experience, particularly of neonatal infections, has a role in forming high anxiety levels in later life. One of the mechanisms of these changes may consist of impairments to the functional activity of ionotropic glutamate receptors associated with rearrangements in their subunit composition. The aim of the present work was to study measures of anxiety and levels of expression of genes for NMDA receptor (Grin1, Grin2a, Grin2b) and AMPA receptor (Gria1, Gria2) subunits in the medial prefrontal cortex, ventral and dorsal parts of the hippocampus in adult rats which at an early age had received bacterial lipopolysaccharide (LPS) at doses inducing the development of neuroinflammatory processes. Gene expression was studied by real-time reverse transcription PCR (qRT-PCR). Administration of LPS at doses of 25 and 50 μg/kg to male Wistar rats on days 15, 18, and 21 of life induced increases in the expression of genes for proinflammatory cytokines IL-1β and tumor necrosis factor in parts of the hippocampus. Increases in the expression of the Grin2b, Gria1, and Gria2 genes in the ventral parts of the hippocampus were seen three months after LPS administration (after injection of 50 μg/kg LPS), as were increases in expression of the Gria2 gene in the dorsal part of the hippocampus (after injection of 25 μg/kg LPS). These changes were accompanied by impairment to exploratory behavior in the open field test and decreased anxiety levels in the elevated plus maze. These studies showed that administration of bacterial LPS in early postnatal ontogeny leads to time-delayed changes in the expression of genes for NMDA and AMPA receptor subunits in the hippocampus and the associated forms of behavior.