Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors
Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors
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DOI：
10.1523/jneurosci.3857-09.2010
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发表时间：
2010-02-17
影响因子：
5.3
通讯作者：
Do, Kim Q.
中科院分区：
文献类型：
--
作者：
Steullet, Pascal;Cabungcal, Jan-Harry;Do, Kim Q.
在精神分裂症中观察到氧化应激升高和抗氧化系统的改变，包括谷胱甘肽（GSH）减少。遗传和功能的数据表明，受损的谷胱甘肽合成代表了一个易感因素的障碍。在这里，我们表明，遗传受损的GSH合成影响海马小白蛋白免疫反应（PV-IR）中间神经元的形态和功能的完整性，已知在精神分裂症中受到影响。GSH缺乏导致腹侧海马CA 3和齿状回（DG）中PV-IR中间神经元选择性减少，而背侧海马则不减少，并伴随β/γ振荡减少。PV-IR中间神经元的损伤出现在青春期结束/成年早期，因为氧化应激增加或选择性累积在腹侧海马的CA 3和DG中。这种氧化还原失调改变了压力和情绪相关的行为，但空间能力完好无损，表明腹侧海马而不是背侧海马的功能中断。因此，GSH缺陷以区域和时间特异性方式影响PV-IR中间神经元的完整性和神经元同步性，导致与精神疾病相关的行为表型。
Elevated oxidative stress and alteration in antioxidant systems, including glutathione (GSH) decrease, are observed in schizophrenia. Genetic and functional data indicate that impaired GSH synthesis represents a susceptibility factor for the disorder. Here, we show that a genetically compromised GSH synthesis affects the morphological and functional integrity of hippocampal parvalbumin-immunoreactive (PV-IR) interneurons, known to be affected in schizophrenia. A GSH deficit causes a selective decrease of PV-IR interneurons in CA3 and dendate gyrus (DG) of the ventral but not dorsal hippocampus and a concomitant reduction of beta/gamma oscillations. Impairment of PV-IR interneurons emerges at the end of adolescence/ early adulthood as oxidative stress increases or cumulates selectively in CA3 and DG of the ventral hippocampus. Such redox dysregulation alters stress and emotion-related behaviors but leaves spatial abilities intact, indicating functional disruption of the ventral but not dorsal hippocampus. Thus, a GSH deficit affects PV-IR interneuron's integrity and neuronal synchrony in a region-and time-specific manner, leading to behavioral phenotypes related to psychiatric disorders.