The effect of maternal infection on cognitive development and hippocampus neuronal apoptosis, proliferation and differentiation in the neonatal rats.

ABSTRACT

Many epidemiological reports stated a strong association between maternal infection and development of cerebral palsy, which is a major cause of cognitive impairment. The pathophysiological mechanism of intrauterine inflammation is complex. Recently, it was demonstrated that inflammation has a modulating effect on adult neurogenesis. In this study, we discovered the effect of maternal infection to hippocampal neuronal apoptosis, proliferation and differentiation, and cognitive development in the developing brains of neonatal rats. Morris water maze test was used to assess learning and memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to determine neuronal apoptosis, immunostaining was conducted to assess neurogenesis, and Western blot for extracellular signal-regulated kinase (ERK), cyclic AMP responsive element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Results demonstrated that maternal infection increased neuronal apoptosis and significantly impaired spatial learning and memory ability. Maternal infection significantly increased cell proliferation, accompanied by an increased expression of ERK (P3-P7), CREB (P3-P7) and BDNF (P3). On P28, there was no significant difference of cell survival and differentiation in two groups. These results suggest that variation in ERK activity and subsequent expression of its downstream targets, including CREB and BDNF might contribute, at least partially, to modulation of inflammation related cell proliferation, survival and differentiation. Maternal infection increased hippocampal neuronal apoptosis and affected cell proliferation and differentiation in neonatal rats, which may be regarded as an etiological factor in cognitive development impairment.