Postnatal nectin-3 knockdown induces structural abnormalities of hippocampal principal neurons and memory deficits in adult mice
Postnatal nectin-3 knockdown induces structural abnormalities of hippocampal principal neurons and memory deficits in adult mice
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出生后 nectin-3 敲低会导致成年小鼠海马主要神经元的结构异常和记忆缺陷
DOI：
10.1002/hipo.23098
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发表时间：
2019-11-01
期刊：
影响因子：
3.5
通讯作者：
Si, Tian-Mei
中科院分区：
文献类型：
--
作者：
Liu, Rui;Wang, Han;Si, Tian-Mei
出生后早期是海马神经发育的关键期，也是易受不良生活经验影响的时期。最近的证据表明，Nectin-3是一种细胞黏附分子，介导了出生后应激诱导的成年海马区记忆功能障碍和树突改变。但尚不清楚仅靠出生后Nextin-3的减少是否足以改变成年后的海马体结构和功能。在这里，我们通过将腺相关病毒(AAV)注射到新生小鼠的侧脑室(出生后第2天)，分别从出生后早期下调了海马区Nectin-3及其异嗜性黏附伙伴Nectin-1的表达。我们发现，从出生后早期抑制Nectin-3的表达，但不抑制Nectin-1的表达，会损害成年小鼠的海马区依赖的新对象识别和空间对象识别。此外，AAV介导的Nectin-3基因敲除显著降低了整个海马区锥体神经元的树突复杂性和棘突密度，而Nectin-1基因敲除仅导致CA3中粗壮的棘突的丢失。我们的数据提供了直接的证据表明，果胶蛋白，尤其是果胶蛋白-3，对于出生后海马体的记忆功能和结构完整性的发育是必需的。
The early postnatal stage is a critical period of hippocampal neurodevelopment and also a period of high vulnerability to adverse life experiences. Recent evidence suggests that nectin-3, a cell adhesion molecule, mediates memory dysfunction and dendritic alterations in the adult hippocampus induced by postnatal stress. But it is unknown whether postnatal nectin-3 reduction alone is sufficient to alter hippocampal structure and function in adulthood. Here, we down regulated hippocampal expression of nectin-3 and its heterophilic adhesion partner nectin-1, respectively, from early postnatal stage by injecting adeno-associated virus (AAV) into the cerebral lateral ventricles of neonatal mice (postnatal day 2). We found that suppression of nectin-3, but not nectin-1, expression from the early postnatal stage impaired hippocampus-dependent novel object recognition and spatial object recognition in adult mice. Moreover, AAV-mediated nectin-3 knockdown significantly reduced dendritic complexity and spine density of pyramidal neurons throughout the hippocampus, whereas nectin-1 knockdown only induced the loss of stubby spines in CA3. Our data provide direct evidence that nectins, especially nectin-3, are necessary for postnatal hippocampal development of memory functions and structural integrity.