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