Aberrant maturation and connectivity of prefrontal cortex in schizophrenia-contribution of NMDA receptor development and hypofunction.
Aberrant maturation and connectivity of prefrontal cortex in schizophrenia-contribution of NMDA receptor development and hypofunction.
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DOI：
10.1038/s41380-021-01196-w
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发表时间：
2022-01
影响因子：
11
通讯作者：
Chamberlin LA
中科院分区：
文献类型：
--
作者：
Gao WJ;Yang SS;Mack NR;Chamberlin LA
精神分裂症的神经生物学涉及病理生理学的多个方面，从其遗传基础到神经化学和神经生理学的变化，到神经回路的系统水平。虽然与神经病理生理学相关的确切机制仍然不清楚，但一个重要的方面是前额叶皮质的异常成熟和连接，导致疾病不同阶段的复杂症状。在这里，我们关注早期发育功能障碍，特别是N-甲基-D-天冬氨酸受体(NMDAR)的发育和功能低下，可能导致前额叶皮质内局部回路和其远程连接的功能障碍。更具体地说，我们将专注于一个假说，即NMDAR在发育过程中如何发挥汇聚点的作用，导致局部伽马-氨基丁酸(GABA)缺乏和前额叶皮质的输入-输出连接障碍，最终导致认知和社会缺陷。文中列出了许多悬而未决的问题和假设机制，为这一耐人寻味的假说的未来研究提供了参考，这可能有助于更好地理解与前额叶皮质相关的异常成熟和连接。
The neurobiology of schizophrenia involves multiple facets of pathophysiology, ranging from its genetic basis over changes in neurochemistry and neurophysiology, to the systemic level of neural circuits. Although the precise mechanisms associated with the neuropathophysiology remain elusive, one essential aspect is the aberrant maturation and connectivity of the prefrontal cortex that leads to complex symptoms in various stages of the disease. Here, we focus on how early developmental dysfunction, especially N-methyl-D-aspartate receptor (NMDAR) development and hypofunction, may lead to the dysfunction of both local circuitry within the prefrontal cortex and its long-range connectivity. More specifically, we will focus on an “all roads lead to Rome” hypothesis, i.e., how NMDAR hypofunction during development acts as a convergence point and leads to local gamma-aminobutyric acid (GABA) deficits and input-output dysconnectivity in the prefrontal cortex, which eventually induce cognitive and social deficits. Many outstanding questions and hypothetical mechanisms are listed for future investigations of this intriguing hypothesis that may lead to a better understanding of the aberrant maturation and connectivity associated with the prefrontal cortex.
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影响因子：
15.9
作者：
Banerjee A;Larsen RS;Philpot BD;Paulsen O
通讯作者：
Paulsen O
影响因子：
3.8
作者：
Bicks LK;Koike H;Akbarian S;Morishita H
通讯作者：
Morishita H
影响因子：
5.3
作者：
Bean, Jonathan C.;Lin, Thiri W.;Mei, Lin
通讯作者：
Mei, Lin
影响因子：
16.2
作者：
Barnes, Samuel J.;Sammons, Rosanna P.;Keck, Tara
通讯作者：
Keck, Tara
内侧丘脑和腹内侧丘脑参与前额皮质中不同的 L1 回路。
影响因子：
16.2
作者：
Anastasiades PG;Collins DP;Carter AG
通讯作者：
Carter AG