Abstract

The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

Highlights

  • The physiological changes that occur during pregnancy in the female mammal include neural adaptations, which have led to the coining of the phrases “expectant brain” or “maternal brain” [1,2]

  • Expression levels in both dopamine D2 and D5 receptors did not change over the course of pregnancy contrary to the array results (p’s > 0.05, Figure 1)

  • Even though the changes in cholinergic genes were not confirmed, together this evidence indicates the possible role for cholinergic neurons in the ventromedial nucleus of the hypothalamus (VMH) in the regulation of another reproductive behavior, maternal behavior, and points to a new avenue of research involving the cholinergic system in pregnancy-induced modifications of the brain

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Summary

Introduction

The physiological changes that occur during pregnancy in the female mammal include neural adaptations, which have led to the coining of the phrases “expectant brain” or “maternal brain” [1,2] These adaptations include changes in stress responsiveness [3], learning and memory [4], preparation for parturition and lactation with alterations in oxytocin and prolactin regulation [5], respectively, and changes in feeding behavior and energy metabolism in favor of the fetus [6,7]. Many of these changes involve the ventromedial nucleus of the hypothalamus (VMH) (e.g., [8]). The objective of the current study was to identify neurotransmitter and neuromodulator genes that may be change from mid-pregnancy (day 12) to late pregnancy (day 21) for the purpose of determining which genes may regulate the changes in the expectant or maternal brain

Results and Discussion
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