Early postnatal stress suppresses the developmental trajectory of hippocampal pyramidal neurons: the role of CRHR1
Early postnatal stress suppresses the developmental trajectory of hippocampal pyramidal neurons: the role of CRHR1
复制标题
产后早期应激抑制海马锥体神经元的发育轨迹：CRHR1的作用
DOI：
10.1007/s00429-016-1182-4
复制
发表时间：
2016-12-01
影响因子：
3.1
通讯作者：
Si, Tian-Mei
中科院分区：
文献类型：
--
作者：
Liu, Rui;Yang, Xiao-Dun;Si, Tian-Mei
生命早期的不良经历阻碍了海马体的发育和成熟，但早期应激如何在不同的生命阶段扰乱海马体的发育轨迹及其潜在的分子机制仍有待研究。在这项研究中，我们从出生后第2天(P2)到P9对雄性小鼠进行了应激，并检测了CRHR1在出生后应激诱导的海马CA3区锥体神经元结构重构中的潜在作用，这些神经元在应激后直接(P9)、青春期中期(P35)和成年(P90)。我们发现，早期应激暴露显著减少了P9和P90上CA3神经元顶端树突的树枝形成和棘突密度。此外，出生后应激的神经元在P35和P90之间经历了更多的脊椎修剪，特别是细刺。这些应激诱导的即刻和长期的结构异常可以在应激暴露期间每天系统地给予CRHR1拮抗剂安塔拉明(20A/g体重)来消除。然而，这样的治疗策略并没有减弱青春期中期对P35的有害应激影响。然后，我们将安非他明治疗延长到出生后第二周结束，发现长期阻断CRHR1可以阻止出生后早期应激对CA3神经元结构重塑的中期影响。我们的研究描述了早期生活应激对海马锥体神经元发育轨迹的影响，并强调了CRHR1在调节早期生活应激引起的这些负面后果中的关键作用。
Adverse experiences early in life hamper the development and maturation of the hippocampus, but how early-life stress perturbs the developmental trajectory of the hippocampus across various life stages and the underlying molecular mechanisms remain to be investigated. In this study, we stressed male mice from postnatal day 2 (P2) to P9, and examined the potential role of CRHR1 in postnatal stress-induced structural remodeling of hippocampal CA3 pyramidal neurons directly after stress (P9), in mid-adolescence (P35) and in adulthood (P90). We found that early-life stress exposure significantly reduced apical dendritic arborization and spine density in CA3 neurons on P9 and P90. Moreover, postnatally stressed neurons underwent increased pruning of spines, especially thin spines, between P35 and P90. These stress-induced immediate and long-term structural abnormalities could be abolished by daily systemic administration of the CRHR1 antagonist antalarmin (20 A mu g/g of body weight) during stress exposure. However, such treatment strategy failed to attenuate the deleterious stress effects in mid-adolescence on P35. We then extended antalarmin treatment until the end of the second postnatal week, and found that prolonged blockade of CRHR1 could prevent the mid-term impact of early postnatal stress on structural remodeling of CA3 neurons. Our study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, and highlighted the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress.