The change in retinoic acid receptor signaling induced by prenatal marginal vitamin A deficiency and its effects on learning and memory

This study investigated the prenatal marginal vitamin A deficiency (mVAD)-related impairment in learning and memory and the interactions between RAR alpha, Src and NR1. Learning and memory were assessed in adult rats that were exposed to prenatal mVAD with Morris water maze. The average escape time was longer in mVAD rats, and they passed the hidden platform fewer times during the memory retention test than normal vitamin A intake (VAN) rats. The mRNA and protein levels of RAR alpha, Src and NR1 in mVAD rats were significantly lower than those in VAN rats. RAR alpha and Src, but not NR1, were in the same protein complex. RA treatment-induced increase in RAR alpha, Src and NR1 expressions in mVAD neurons was much lower than that in VAN neurons. Overexpression of RAR alpha gene in VAN neurons induced an increase in RAR alpha, Src and NR1 expressions, while silencing of RAR alpha gene induced a decrease in expressions of RAR alpha and Src, but not that of of NR1. In mVAD neurons, however, overexpression of RAR alpha did not induce an increase in NR1 expression, while silencing of RAR alpha gene had no effect on Src and NR1 expressions. Furthermore, inhibition of Src was associated with a decrease in NR1 expression but not that of RAR alpha. Prenatal mVAD was associated with impaired learning and memory in adult rats. It is possible that mVAD-related decrease in RAR alpha led to a decrease in Src expression, which in turn down-regulated NR1 expression and Ca2+ influx and eventually caused learning and memory deficits. (C) 2017 Elsevier Inc. All rights reserved.