Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development.
Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development.
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DOI：
10.1186/s13293-017-0142-x
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发表时间：
2017
影响因子：
7.9
通讯作者：
Galea LAM
中科院分区：
文献类型：
--
作者：
Gobinath AR;Workman JL;Chow C;Lieblich SE;Galea LAM
产后抑郁症影响着大约15%的母亲，并代表着发育中的后代的早期生活逆境。产后抑郁症可以用处方抗抑郁药治疗，如氟西汀（FLX）。然而，FLX可以在母乳中保持活性，引起了对新生儿FLX暴露后果的担忧。海马体对发育压力高度敏感，男性和女性在许多端点对压力的反应不同，包括海马体的可塑性。然而，目前尚不清楚发育暴露于FLX如何改变海马发育的轨迹。本研究的目的是研究母体产后皮质酮（CORT，产后抑郁症模型）和并发FLX对雄性和雌性后代海马神经发生的长期影响。雌性Sprague-Dawley大鼠母鼠在产后第2-23天每天用CORT或油和FLX或盐水处理。在出生后第31天（青春期前）、出生后第42天（青春期）和出生后第69天（成年）灌注后代。在背侧和腹侧海马中，处理组织用于双皮质素（DCX），其是未成熟神经元的内源性标记物。母亲产后CORT降低了青春期前男性背海马中DCX表达细胞的密度，并增加了青春期男性的密度，这表明产后CORT暴露破坏了DCX表达细胞密度的典型进展。此外，在油处理的母鼠的后代中，青春期前的雄性比青春期前的雌性具有更大密度的DCX表达细胞，并且母体产后CORT防止了这种性别差异。在青春期前的女性中，与生理盐水相比，母亲产后FLX降低了背海马中DCX表达细胞的密度。正如预期的那样，母体CORT降低了成年雌性后代中表达DCX的细胞的密度，但对雄性后代没有影响。无论性别或年龄，母亲产后CORT/FLX的组合减少背海马中DCX表达细胞的密度。这些研究结果揭示了用FLX对产后抑郁症进行建模治疗如何根据性别不同改变发育中后代的海马神经发生，主要是在背侧齿状回和生命早期。
Postpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Postpartum depression can be treated with prescription antidepressants like fluoxetine (FLX). However, FLX can remain active in breast milk, raising concerns about the consequences of neonatal FLX exposure. The hippocampus is highly sensitive to developmental stress, and males and females respond differently to stress at many endpoints, including hippocampal plasticity. However, it is unclear how developmental exposure to FLX alters the trajectory of hippocampal development. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum depression) and concurrent FLX on hippocampal neurogenesis in male and female offspring. Female Sprague-Dawley rat dams were treated daily with either CORT or oil and FLX or saline from postpartum days 2–23. Offspring were perfused on postnatal day 31 (pre-adolescent), postnatal day 42 (adolescent), and postnatal day 69 (adult). Tissue was processed for doublecortin (DCX), an endogenous marker of immature neurons, in the dorsal and ventral hippocampus. Maternal postpartum CORT reduced density of DCX-expressing cells in the dorsal hippocampus of pre-adolescent males and increased it in adolescent males, suggesting that postpartum CORT exposure disrupted the typical progression of the density of DCX-expressing cells. Further, among offspring of oil-treated dams, pre-adolescent males had greater density of DCX-expressing cells than pre-adolescent females, and maternal postpartum CORT prevented this sex difference. In pre-adolescent females, maternal postpartum FLX decreased the density of DCX-expressing cells in the dorsal hippocampus compared to saline. As expected, maternal CORT reduced the density of DCX-expressing cells in adult female, but not male, offspring. The combination of maternal postpartum CORT/FLX diminished density of DCX-expressing cells in dorsal hippocampus regardless of sex or age. These findings reveal how modeling treatment of postpartum depression with FLX alters hippocampal neurogenesis in developing offspring differently depending on sex, predominantly in the dorsal dentate gyrus and earlier in life.