OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory.
OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory.
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DOI：
10.1093/braincomms/fcaa101
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发表时间：
2020
影响因子：
4.8
通讯作者：
Erchova I
中科院分区：
文献类型：
--
作者：
Bevan RJ;Williams PA;Waters CT;Thirgood R;Mui A;Seto S;Good M;Morgan JE;Votruba M;Erchova I
健康的线粒体网络对于维持神经元突触的完整性是必不可少的。线粒体和代谢功能障碍有助于许多神经退行性疾病包括痴呆的发病机制。OPA 1是线粒体融合和分裂的主要调节因子，并且可能在神经退行性事件中发挥重要作用。为了探索这一点，我们量化了携带Opa 1 Q285 X突变（B6; C3-Opa 1 Q285 STOP; Opa 1 +/−）的老龄Opa 1单倍不足小鼠的海马树突和突触完整性以及学习和记忆表现。我们证明，Opa 1的杂合丢失导致海马锥体CA 1神经元中与年龄相关的提前丢失棘，并导致海马中突触密度降低。这种损失与空间新奇和物体识别方面的微妙记忆缺陷有关。我们假设，代谢失败，以维持正常的神经元活动在一个单一的脊椎水平导致过早的年龄相关的记忆缺陷。这些结果强调了线粒体稳态对衰老过程中神经元功能维持的重要性。线粒体产生记忆功能所需的能量。具有能量产生所必需的遗传减少量的OPA 1蛋白的老年小鼠在行为记忆中具有微妙但持续的缺陷。对相关脑区（海马CA 1）的解剖学检查显示，这些变化影响了细胞之间的通讯，并导致过早的年龄相关记忆缺陷。
A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing. Mitochondria generate energy required for memory function. Aged mice having genetically reduced amount of OPA1 protein necessary for energy production have subtle but persistent deficits in behavioural memory. Anatomical examination of the relevant brain region (hippocampal CA1) revealed changes affecting communication between cells and leading to premature age-related memory deficits.
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影响因子：
4.4
作者：
Bocca, Cinzia;Nzoughet, Judith Kouassi;Reynier, Pascal
通讯作者：
Reynier, Pascal
影响因子：
11.2
作者：
Carelli, Valerio;Musumeci, Olimpia;Caporali, Leonardo;Zanna, Claudia;La Morgia, Chiara;Del Dotto, Valentina;Porcelli, Anna Maria;Rugolo, Michela;Valentino, Maria Lucia;Iommarini, Luisa;Maresca, Alessandra;Barboni, Piero;Carbonelli, Michele;Trombetta, Costantino;Valente, Enza Maria;Patergnani, Simone;Giorgi, Carlotta;Pinton, Paolo;Rizzo, Giovanni;Tonon, Caterina;Lodi, Raffaele;Avoni, Patrizia;Liguori, Rocco;Baruzzi, Agostino;Toscano, Antonio;Zeviani, Massimo
通讯作者：
Zeviani, Massimo
DOI：
10.1111/ejn.13295
发表时间：
2016-08
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Binley KE;Ng WS;Barde YA;Song B;Morgan JE
通讯作者：
Morgan JE
影响因子：
3.4
作者：
Ayzenshtat I;Jackson J;Yuste R
通讯作者：
Yuste R
影响因子：
4.5
作者：
Atamna, Hani;Tenore, Alfred;Dhahbi, Joseph M.
通讯作者：
Dhahbi, Joseph M.