The fate of interneurons, GABA(A) receptor sub-types and perineuronal nets in Alzheimer's disease.
The fate of interneurons, GABA(A) receptor sub-types and perineuronal nets in Alzheimer's disease.
复制标题
DOI：
10.1111/bpa.13129
复制
发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病（AD）是最常见的神经系统疾病，其与逐渐的记忆丧失相关，并且与突触活动过度和异常振荡节律性脑活动相关，所述异常振荡节律性脑活动先于表型改变并且部分地导致疾病病理学的传播。突触过度活跃被认为是由于阶段性和紧张性突触抑制的稳态改变，其由GABAA抑制系统协调，包括中间神经元和GABAA受体的亚类，其在认知功能（包括学习和记忆）中起重要作用。此外，细胞外基质，即神经元周网（PNN），在AD病理学的考虑中经常被忽视，封装了关键脑区域中的抑制性细胞和神经突，最近由于其在突触稳定和兴奋-抑制平衡中的关键作用而受到关注，并且当被破坏时，作为AD相关突触失衡的潜在触发因素。因此，在这篇综述中，我们总结了目前的理解不同的中间神经元亚型的选择性脆弱性，其突触和突触外GABAAR亚型，以及在PNNs在AD的变化，详细说明其对疾病发展的机制的贡献。我们的目标是强调如何看似独特的功能障碍，在每个组件的神经元间GABA抑制系统可以绑在一起，导致严重的电路功能障碍，导致不可逆的症状性损害AD中观察到的。
Alzheimer's disease (AD) is the most common neurological disease, which is associated with gradual memory loss and correlated with synaptic hyperactivity and abnormal oscillatory rhythmic brain activity that precedes phenotypic alterations and is partly responsible for the spread of the disease pathology. Synaptic hyperactivity is thought to be because of alteration in the homeostasis of phasic and tonic synaptic inhibition, which is orchestrated by the GABAA inhibitory system, encompassing subclasses of interneurons and GABAA receptors, which play a vital role in cognitive functions, including learning and memory. Furthermore, the extracellular matrix, the perineuronal nets (PNNs) which often go unnoticed in considerations of AD pathology, encapsulate the inhibitory cells and neurites in critical brain regions and have recently come under the light for their crucial role in synaptic stabilisation and excitatory‐inhibitory balance and when disrupted, serve as a potential trigger for AD‐associated synaptic imbalance. Therefore, in this review, we summarise the current understanding of the selective vulnerability of distinct interneuron subtypes, their synaptic and extrasynaptic GABAAR subtypes as well as the changes in PNNs in AD, detailing their contribution to the mechanisms of disease development. We aim to highlight how seemingly unique malfunction in each component of the interneuronal GABA inhibitory system can be tied together to result in critical circuit dysfunction, leading to the irreversible symptomatic damage observed in AD.
登录
查看更多内容
影响因子：
3.7
作者：
Ali, Afia B.;Thomson, Alex M.
通讯作者：
Thomson, Alex M.
DOI：
10.1073/pnas.96.17.9891
发表时间：
1999-08-17
影响因子：
11.1
作者：
Bonnert, TP;McKernan, RM;Whiting, PJ
通讯作者：
Whiting, PJ
影响因子：
34.7
作者：
Ascoli, Giorgio A.;Alonso-Nanclares, Lidia;Anderson, Stewart A.;Barrionuevo, German;Benavides-Piccione, Ruth;Burkhalter, Andreas;Buzsaki, Gyoergy;Cauli, Bruno;DeFelipe, Javier;Fairen, Alfonso;Feldmeyer, Dirk;Fishell, Gord;Fregnac, Yves;Freund, Tamas F.;Gardner, Daniel;Gardner, Esther P.;Goldberg, Jesse H.;Helmstaedter, Moritz;Hestrin, Shaul;Karube, Fuyuki;Kisvarday, Zoltan F.;Lambolez, Bertrand;Lewis, David A.;Marin, Oscar;Markram, Henry;Munoz, Alberto;Packer, Adam;Petersen, Carl C. H.;Rockland, Kathleen S.;Rossier, Jean;Rudy, Bernardo;Somogyi, Peter;Staiger, Jochen F.;Tamas, Gabor;Thomson, Alex M.;Toledo-Rodriguez, Maria;Wang, Yun;West, David C.;Yuste, Rafael
通讯作者：
Yuste, Rafael
影响因子：
4
作者：
Alcaide, Julia;Guirado, Ramon;Nacher, Juan
通讯作者：
Nacher, Juan
影响因子：
5.6
作者：
Carulli D;Verhaagen J
通讯作者：
Verhaagen J