Expression of synaptophysin and BDNF in the medial prefrontal cortex following early life stress and neonatal hypoxia-ischemia.

Abstract

This study aims at investigating whether early stress interacts with brain injury due to neonatal hypoxia-ischemia (HI). To this end, we examined possible changes in synaptophysin (SYN) and brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC) of maternally separated rats that were subsequently exposed to a HI episode. Rat pups (n=11) were maternally separated during postnatal days 1 to 6 (3hr/day), while another group was left undisturbed (n=11). On postnatal day 7, a subgroup (n=12) from each postnatal manipulation was exposed to HI. Synaptophysin and BDNF expression was estimated in mPFC prelimbic and anterior cingulate subregions of the ipsilateral and contralateral to the occluded common carotid artery hemispheres. Maternally separated rats expressed significantly less BDNF and SYN in both hemispheres. Neonatal HI significantly reduced BDNF and SYN expression in the ipsilateral mPFC only and this reduction was not further altered by early stress. Our findings indicate the enduring negative effect of a short period of maternal separation on the expression of mPFC SYN and BDNF. They, also, reveal that the HI-associated decreases in these markers are limited to the ipsilateral mPFC and are not exacerbated by early stress. These decreases may have important functional implications given the role of prefrontal area in high-order cognition.