Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe.
Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe.
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孕产和婴儿接触调节血清素能中脑背侧的神经可塑性。
DOI：
10.1016/j.psyneuen.2016.10.023
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发表时间：
2017-02
影响因子：
3.7
通讯作者：
Lonstein JS
中科院分区：
文献类型：
--
作者：
Holschbach MA;Lonstein JS
成年人的大脑在激素和受其影响的社会情绪变化的反应中表现出显著的神经可塑性。在有生育和母性经验的女性中，这种神经可塑性包括前脑几个区域中新细胞和现有细胞的出生和死亡，这些区域涉及母性照顾和产后情感状态。然而，对这些过程至关重要的中脑部位的这种可塑性从未被研究过。可视化溴脱氧尿苷（BrdU）标记有丝分裂细胞，l NeuroD标记神经元前体，TUNEL标记死亡细胞，我们发现中脑中缝背核（DR，大多数上升5 -羟色胺能投射的来源）在母性反应中表现出显著的神经可塑性。具体来说，BrdU分析揭示了DR新生细胞的存活（而不是增殖）受生殖状态的调节，因此产后早期出生的细胞与妊娠后期出生的细胞相比，存活的可能性更低。DR中的许多存活细胞具有NeuN免疫反应性，提示神经元表型。同样，产后晚期大鼠的神经免疫反应性DR细胞少于产后早期大鼠。产妇经历有助于产后后期DR新生儿细胞存活率的降低，因为在分娩时去除胎屑增加了细胞存活率，减少了细胞死亡。与母体海马的细胞发生不同，母体海马的细胞发生因循环糖皮质激素而减少，产后肾上腺切除术对DR新生儿细胞存活没有影响。这些生殖状态和母性对DR可塑性的影响与5-羟色胺前体5-羟色胺及其代谢物5-HIAA在DR水平的同步变化有关。我们的研究结果首次证明了细胞发生在任何成年哺乳动物的中脑后脑，后脑可塑性受雌性生殖状态和母性经验的影响，并且这种可塑性伴随着后脑血清素功能的变化。由于血清素对产后护理行为和母亲的情感状态至关重要，DR的神经可塑性变化可能有助于成功母性所必需的神经化学变化。
The adult brain shows remarkable neuroplasticity in response to hormones and the socioemotional modifications that they influence. In females with reproductive and maternal experience, this neuroplasticity includes the birth and death of new and existing cells in several forebrain regions involved in maternal caregiving and postpartum affective state. Such plasticity in midbrain sites critical for these processes has never been examined, though. Visualizing bromodeoxyuridine (BrdU) to label mitotic cells, l NeuroD for neuronal precursors, and TUNEL to identify dying cells, we found that the midbrain dorsal raphe nucleus (DR, the source of most ascending serotoninergic projections) exhibited significant neuroplasticity in response to motherhood. Specifically, BrdU analyses revealed that DR newborn cell survival (but not proliferation) was regulated by reproductive state, such that cells born early postpartum were less likely to survive compared to cells born during late pregnancy. Many of the surviving cells in the DR were NeuN immunoreactive, suggesting a neuronal phenotype. Similarly, late postpartum rats had fewer NeuroD-immunoreactive DR cells than early postpartum rats. Maternal experience contributed to the late postpartum reduction in DR newborn cell survival because removing the litter at parturition increased cell survival and reduced cell death. Unlike cytogenesis in the maternal hippocampus, which is reduced by circulating glucocorticoids, DR newborn cell survival was unaffected by postpartum adrenalectomy. These effects of reproductive state and motherhood on DR plasticity were associated with concurrent changes in DR levels of serotonin's precursor, 5-HTP, and its metabolite, 5-HIAA. Our results demonstrate for the first time that cytogenesis occurs in the midbrain DR of any adult mammal, that DR plasticity is influenced by female reproductive state and maternal experience, and that this plasticity is accompanied by changes in DR serotonergic function. Because serotonin is critical for postpartum caregiving behaviors and maternal affective state, neuroplastic changes in the DR may contribute to the neurochemical changes necessary for successful motherhood.