Elsevier

Neuroscience Letters

Volume 641, 22 February 2017, Pages 21-25
Neuroscience Letters

Research article
Decrease in neuronal spine density in the postpartum period in the amygdala and bed nucleus of the stria terminalis in rat

https://doi.org/10.1016/j.neulet.2017.01.040Get rights and content

Highlights

  • Spine density in the (extended) amygdala was investigated in the peripartum period in rat.

  • The spine density was significantly decreased at 4 days after delivery.

  • The presence of pups after delivery influenced the spine density in the BNST.

Abstract

In pregnancy and the postpartum period, many women have emotional instability and some suffer from depression. The ovarian steroid hormone milieu is markedly changed during these periods, and this hormonal change may be an important cause of peripartum emotional instability. The amygdala is a central region of emotion, and the bed nucleus of the stria terminalis (BNST), which is considered to be the extended amygdala, is also involved in the emotional response. The amygdala and BNST are well characterized as target brain regions for ovarian steroid hormones, and this suggests that the functional response of neurons in these regions to hormonal fluctuation is affected in the peripartum period. In this study, we investigated the neuronal morphology in the central (CeA) and basolateral (BLA) nucleus of the amygdala and BNST on gestational days 15 (G15) (mid-gestation) and 20 (G20) (late gestation) and 4 days after delivery (P4) (early postpartum) in rat. Golgi staining showed that the dendritic spine density, and particularly the number of mature mushroom-type spines, in the CeA, BLA and BNST was significantly decreased at P4, compared with G15 and G20 and with virgin females in the estrous phase in the normal estrous cycle (Est). Interestingly, the presence of pups after delivery influenced the spine density in the BNST. The density was significantly decreased with pup presence compared with pup absence at P4, and compared with G15, G20 and Est. These results provide fundamental insights into the neuronal basis underlying emotional instability during pregnancy and postpartum.

Introduction

During pregnancy, women may have emotional sensitivity, increased anxiety, and emotional instability, such as mood, irritability and anxiety, from the first trimester to a few months after delivery [1], [2]. This emotional instability frequently deviates from the healthy range and falls into a pathological state. The postpartum period is the time of highest risk for development of depression, and the rate of postpartum depression is estimated to be 15% [3], [4], [5]. There is also evidence that depression is as common during pregnancy as postpartum [6], [7], [8], whereas anxiety generally tends to decrease throughout pregnancy [2], [9], [10].

Reproduction is associated with alterations in hormonal secretion [11]. Pregnancy, parturition and lactation result in dramatic changes in the neuroendocrine axis [2], [12]. Ovarian steroid hormones (estrogen and progestogens) play important roles in maintenance of pregnancy, and the concentrations of these hormones in blood are increased by the developing placenta and reach much higher levels than in the normal sexual cycle [13]. After parturition, loss of the placenta results in a sudden decrease in circulating hormone levels. Estrogen and progesterone influence emotions and contribute to sex differences and variations in behavior in the sexual cycle [14], [15]. Several studies have shown significant changes in anxiety-like behavior upon administration of estrogen and/or progesterone in rodent models [16], [17].

Sex steroid fluctuations in the peripartum period are believed to play an important role in establishment of depressive symptoms due to changes in neural function and synaptic connectivity in brain regions regulating emotions [2], [9], [10], [18], [19]. The amygdala is an important nuclear complex that regulates emotional responses [20], [21]. Neuroanatomically, the central nucleus (CeA) and basolateral nucleus (BLA) of the amygdala are particularly concerned with stress, fear and anxiety responses, as well as depressive symptoms [22], [23], [24]. The bed nucleus of the stria terminalis (BNST), which receives strong projections from the basolateral amygdala and is considered to be the extended amygdala, is also involved in anxiety and stress responses, including depressive-like behaviors, in rodent models [23], [25], [26], [27]. The BLA, CeA and BNST express ovarian steroid hormone receptors [28], [29] and contribute to regulation of sexually differentiated brain functions. These findings suggest that neurons in the BLA, CeA and BNST may be affected by changes in the peripartum hormonal milieu. In this study, we examined neuronal spine density during pregnancy and early postpartum in the amygdala and BNST of rat.

Section snippets

Animals

Nulliparous female Wistar rats aged 12 weeks and primiparous pregnant Wistar rats were purchased from Shimizu Laboratory Supplies Co (Kyoto, Japan) and housed in plastic cages with standard bedding and continuous access to food and water. The temperature was maintained at 22 °C with a 12-h light/dark cycle. Vaginal smears were taken from the nulliparous female rats to determine the ovarian cycle. The committee for Animal Research of Kyoto Prefectural University of Medicine authorized all animal

Results

The total spine density in the CeA (Fig. 2) at P4(+) was significantly lower than those at G15, G20 and Est, and that at P4(−) was significantly lower than at G20. Similarly, the mushroom-type spine density in the CeA at P4(+) was significantly lower than those at G15, G20 and Est, and that at P4(−) was significantly lower than at G20. The total spine density and the mushroom-type spine density in the BLA (Fig. 3) at P4(+) and P4(−) were significantly lower than those at G15, G20 and Est. The

Discussion

In this study, changes in dendritic spine density in brain areas involved in emotional regulation were examined to evaluate the correlation of neuronal function with emotional instability during pregnancy and puerperium [2]. This is the first report to show a difference in the neuronal morphology of the CeA, BLA and BNST at 4 days after delivery, compared to the normal estrous cycle and during gestation. Neurons in the motor area of the cerebral cortex did not show an alteration of spine

Support or grant information

This work was supported by JSPS KAKENHI Grant Number JP23500396.

Acknowledgement

We thank Dr. Shinji Tsukahara (Saitama University) for technical advice.

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