Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits.
Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits.
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DOI：
10.1038/s41398-022-01908-y
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发表时间：
2022-04-04
影响因子：
6.8
通讯作者：
Wang XD
中科院分区：
文献类型：
--
作者：
Wu C;Gong Q;Xu X;Fang P;Wang C;Yu JY;Wang XX;Fang SH;Chen WJ;Lou HF;Liu YH;Wang L;Liu YJ;Chen W;Wang XD
细胞黏附分子Nectin3及其突触前伙伴Nectin1与早期生活应激相关的认知障碍有关，但Nextin1-Nectin3系统如何在应激诱导的神经元、回路和认知异常中起作用仍有待研究。在这里，我们发现，在新生应激雄性小鼠中，需要内侧嗅觉皮质(MEC)-CA1通路的时间顺序和空间工作记忆以及CA1锥体神经元的结构完整性在成年后明显受损。应激小鼠的这些认知和结构异常与内嗅区和海马亚区的Nextin水平降低有关，特别是MEC中的Nextin 1和CA1中的Nextin 3的水平降低。出生后抑制MEC中的Nectin 1而不是Nectin 3水平会损害空间记忆，而MEC兴奋性神经元中Nectin 1的条件失活复制了早期应激对MEC依赖的记忆和CA1中神经元可塑性的不利影响。我们的数据表明，早期应激破坏了突触前Nexin1介导的MEC-CA1通路中的神经元间黏附，这可能反过来导致应激诱导的突触和认知障碍。
The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired in adulthood. These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the MEC and nectin3 level in the CA1. Postnatal suppression of nectin1 but not nectin3 level in the MEC impaired spatial memory, whereas conditional inactivation of nectin1 from MEC excitatory neurons reproduced the adverse effects of early-life stress on MEC-dependent memories and neuronal plasticity in CA1. Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits.
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影响因子：
2.7
作者：
Arp, J. Marit;ter Horst, Judith P.;Krugers, Harm J.
通讯作者：
Krugers, Harm J.
影响因子：
3
作者：
Ganea, K.;Liebl, C.;Schmidt, M. V.
通讯作者：
Schmidt, M. V.
影响因子：
5
作者：
Bath KG;Nitenson AS;Lichtman E;Lopez C;Chen W;Gallo M;Goodwill H;Manzano-Nieves G
通讯作者：
Manzano-Nieves G
突触细胞粘附。
影响因子：
7.2
作者：
Missler M;Südhof TC;Biederer T
通讯作者：
Biederer T
阻断促肾上腺皮质激素释放激素受体 1 可减轻生命早期应激引起的新生儿海马突触异常
影响因子：
3.5
作者：
Liao, Xue-Mei;Yang, Xiao-Dun;Wang, Xiao-Dong
通讯作者：
Wang, Xiao-Dong