91. Early-life LPS administrations induce cognitive decline and changes in NMDA receptor subunit gene expression in the rodent brain

Abstract

The aim of this work was to investigate the effect of neonatal bacterial infections on NMDA receptor subunit composition underlying exploratory behavior and spatial memory. Male Wistar rats were treated with saline or bacterial lipopolysaccharide (LPS, 25 μ/kg) intraperitoneally at PND 14, 16, and 18, and a control group was left intact. Behavioral testing was performed on PND 22–29 in the Open Field and the Morris water maze. The mRNA expression of NR1, NR2A, NR2B, NR2C, and NR2D subunits of NMDA receptors in medial prefrontal cortex (MPC), dorsal and ventral hippocampus (DH, VH) of 23-day-old rats was measured using qRT-PCR. The subjects treated with LPS exhibited impaired exploratory behavior in the Open Field. Increased variability in the long-term spatial memory of treated rats was revealed in the Morris water maze. The behavioral abnormalities were accompanied by decreased NR2B, NR2C mRNA expression in VH, DH, and MPC, and decreased NR1 mRNA in the MPC versus intact group. The level of NR2D mRNA increased in the DH. The comparison of experimental and saline groups revealed the decrease of NR2C mRNA expression in the MPC. Thus, the LPS-induced impairments of behavior may be associated with altered subunit composition of the NMDA receptor. These results identify a potential receptor target for future research investigating the cognitive dysfunctions caused by neonatal infections.