Anxiety induced by prenatal stress is associated with suppression of hippocampal genes involved in synaptic function


Address correspondence and reprint requests to Marta Weinstock, Department of Pharmacology, School of Pharmacy, Hebrew University, Ein Kerem, Jerusalem 91120, Israel. E-mail:


Exposure of pregnant women or animals to stress during a critical period of foetal brain development increases the likelihood of anxiety, depression and learning deficits that are associated with structural alterations in the offspring hippocampus. In this study, we report the effect of gestational stress in rats on anxiogenic behaviour and hippocampal gene expression of their 23-day-old female offspring. As the rat brain continues to develop after birth, we also used the procedure of handling (H) during the first 10 days of life to reverse the anxiogenic behaviour of prenatally stressed (PS) rats. By means of micro-array analysis on hippocampal extracts, we found that the expression of about 6.1% of 9505 valid genes was significantly altered by prenatal stress (p < 0.05). Of these, 48% were over-expressed and 52% under-expressed. The latter included ∼300 genes that participate in axonal growth, regulation of ion channels and transporters, trafficking of synaptic vesicles and neurotransmitter release. About 30% of the genes that were down-regulated in PS rats were restored to control levels by H. These include genes that play a role in pre-synaptic organization and function. Our results provide a possible relationship between hippocampal gene expression and changes in behaviour resulting from prenatal stress.