Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives.
Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives.
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DOI：
10.1016/j.biopsych.2017.05.024
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发表时间：
2017-10-15
影响因子：
10.6
通讯作者：
Sibille E
中科院分区：
文献类型：
--
作者：
Fee C;Banasr M;Sibille E
外部和内部信号的功能整合构成了信息加工的基础，是高级认知功能的必要条件。这发生在微调的皮质微回路中，其功能在细胞水平上由兴奋性谷氨酸能锥体神经元和抑制性γ-氨基丁酸（GABA）中间神经元平衡。从细胞过程到神经网络活动，兴奋和抑制的平衡在多种神经精神疾病中被典型地破坏，包括重度抑郁症（MDD）、双相情感障碍（BPD）、焦虑症和精神分裂症（SCZ）。具体来说，近三十年的研究表明，抑制性GABA水平和功能的降低在疾病中的作用。在MDD中，最近来自人类死后和动物研究的证据表明，共同表达神经肽生长抑素的gaba能中间神经元（“SST细胞/中间神经元”）具有选择性易感性。细胞类型特异性分子遗传学的进展已经帮助阐明了SST中间神经元在皮层加工（锥体细胞兴奋性输入的调节）和行为控制（情绪和认知）中的几个重要作用。在这里，我们回顾了障碍中gaba能缺陷引起的抑制功能改变的证据，特别是在重度抑郁症中。然后，我们将重点放在皮层微回路的特性上，其中sst阳性GABA中间神经元缺陷可能以多种方式破坏功能。最后，我们根据最近的研究讨论了SST细胞缺陷的假定起源，以及对治疗方法的影响。我们得出结论，SST中间神经元的缺陷代表了一种有贡献的细胞病理，因此是MDD和其他SST细胞和GABA功能降低的疾病中抑制功能改变正常化的有希望的靶点。
The functional integration of external and internal signals forms the basis of information processing and is essential for higher cognitive functions. This occurs in finely-tuned cortical microcircuits whose functions are balanced at the cellular level by excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons. The balance of excitation and inhibition, from cellular processes to neural network activity, is characteristically disrupted in multiple neuropsychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BPD), anxiety disorders, and schizophrenia (SCZ). Specifically, nearly three decades of research demonstrate a role for reduced inhibitory GABA level and function across disorders. In MDD, recent evidence from human postmortem and animal studies suggests a selective vulnerability of GABAergic interneurons that co-express the neuropeptide somatostatin (“SST cells/interneurons”). Advances in cell type-specific molecular genetics have now helped to elucidate several important roles for SST interneurons in cortical processing (regulation of pyramidal cell excitatory input) and behavioral control (mood and cognition). Here, we review evidence for altered inhibitory function arising from GABAergic deficits across disorders, and specifically in MDD. We then focus on properties of the cortical microcircuit, wherein SST-positive GABA interneuron deficits may disrupt functioning in several ways. Finally, we discuss the putative origins of SST cell deficits, as informed by recent research, and implications for therapeutic approaches. We conclude that deficits in SST interneurons represent a contributing cellular pathology, and therefore a promising target for normalizing altered inhibitory function in MDD and other disorders with reduced SST cell and GABA functions.
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影响因子：
11
作者：
Chowdhury GM;Zhang J;Thomas M;Banasr M;Ma X;Pittman B;Bristow L;Schaeffer E;Duman RS;Rothman DL;Behar KL;Sanacora G
通讯作者：
Sanacora G
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
3.7
作者：
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通讯作者：
Thomson, Alex M.
影响因子：
4.3
作者：
Dubin, Marc J.;Mao, Xiangling;Shungu, Dikoma C.
通讯作者：
Shungu, Dikoma C.
影响因子：
11
作者：
Carreno, F. R.;Donegan, J. J.;Lodge, D. J.
通讯作者：
Lodge, D. J.