Ambra1 Shapes Hippocampal Inhibition/Excitation Balance: Role in Neurodevelopmental Disorders.
Ambra1 Shapes Hippocampal Inhibition/Excitation Balance: Role in Neurodevelopmental Disorders.
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DOI：
10.1007/s12035-018-0911-5
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发表时间：
2018-10
影响因子：
5.1
通讯作者：
D'Amelio M
中科院分区：
文献类型：
--
作者：
Nobili A;Krashia P;Cordella A;La Barbera L;Dell'Acqua MC;Caruso A;Pignataro A;Marino R;Sciarra F;Biamonte F;Scattoni ML;Ammassari-Teule M;Cecconi F;Berretta N;Keller F;Mercuri NB;D'Amelio M
兴奋性和抑制性突触传递之间的不平衡导致脑网络功能障碍，是神经发育障碍发病机制的核心。小白蛋白中间神经元与这种不平衡密切相关。在这里，我们探讨了携带Ambra1单倍体缺陷的小鼠的社会行为和海马功能，Ambra1是一种对大脑发育至关重要的促自噬基因。我们发现杂合子Ambra1小鼠（Ambra+/−）的特征是海马小白蛋白中间神经元的缺失，抑制/兴奋比的降低，以及仅限于雌性的社会行为的改变。Ambra1+/−雌性小白蛋白中间神经元的缺失与主要神经元抑制驱动的减少以及网络振荡活动、CA1突触可塑性和锥体神经元脊柱密度的改变进一步相关。内侧神经节隆起的祖神经元在胚胎发育过程中凋亡的增加强调了小白蛋白中间神经元的损失。总之，这些发现确定了一种依赖ambra1的机制，该机制驱动海马体中的抑制/兴奋失衡，导致异常的大脑活动，使人联想到神经发育障碍。本文的在线版本（10.1007/s12035-018-0911-5）包含补充材料，授权用户可以使用。
Imbalances between excitatory and inhibitory synaptic transmission cause brain network dysfunction and are central to the pathogenesis of neurodevelopmental disorders. Parvalbumin interneurons are highly implicated in this imbalance. Here, we probed the social behavior and hippocampal function of mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene crucial for brain development. We show that heterozygous Ambra1 mice (Ambra+/−) are characterized by loss of hippocampal parvalbumin interneurons, decreases in the inhibition/excitation ratio, and altered social behaviors that are solely restricted to the female gender. Loss of parvalbumin interneurons in Ambra1+/− females is further linked to reductions of the inhibitory drive onto principal neurons and alterations in network oscillatory activity, CA1 synaptic plasticity, and pyramidal neuron spine density. Parvalbumin interneuron loss is underlined by increased apoptosis during the embryonic development of progenitor neurons in the medial ganglionic eminence. Together, these findings identify an Ambra1-dependent mechanism that drives inhibition/excitation imbalance in the hippocampus, contributing to abnormal brain activity reminiscent of neurodevelopmental disorders. The online version of this article (10.1007/s12035-018-0911-5) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Fimia, Gian Maria;Stoykova, Anastassia;Cecconi, Francesco
通讯作者：
Cecconi, Francesco
影响因子：
3.4
作者：
Krashia, Paraskevi;Martini, Alessandro;Mercuri, Nicola Biagio
通讯作者：
Mercuri, Nicola Biagio
DOI：
10.1016/s0169-328x(03)00339-5
发表时间：
2003-10-21
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Dewing, P;Shi, T;Vilain, E
通讯作者：
Vilain, E
影响因子：
4.5
作者：
Eack SM;Bahorik AL;McKnight SA;Hogarty SS;Greenwald DP;Newhill CE;Phillips ML;Keshavan MS;Minshew NJ
通讯作者：
Minshew NJ
影响因子：
6.2
作者：
Halladay AK;Bishop S;Constantino JN;Daniels AM;Koenig K;Palmer K;Messinger D;Pelphrey K;Sanders SJ;Singer AT;Taylor JL;Szatmari P
通讯作者：
Szatmari P