Social isolation exacerbates schizophrenia-like phenotypes via oxidative stress in cortical interneurons.
Social isolation exacerbates schizophrenia-like phenotypes via oxidative stress in cortical interneurons.
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DOI：
10.1016/j.biopsych.2012.12.004
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发表时间：
2013-05-15
影响因子：
10.6
通讯作者：
Nakazawa, Kazu
中科院分区：
文献类型：
--
作者：
Jiang, Zhihong;Rompala, Gregory R.;Zhang, Shuqin;Cowell, Rita M.;Nakazawa, Kazu
关键词：
Our previous studies indicated that NMDA receptor (NMDAR) deletion from a subset of corticolimbic interneurons in the mouse brain during early postnatal development is sufficient to trigger several behavioral and pathophysiological features resembling the symptoms of human schizophrenia. Interestingly, many of these behavioral phenotypes are exacerbated by social isolation stress. However, the mechanisms underlying the exacerbating effects of social isolation are unclear. Using GABAergic interneuron-specific NMDAR hypofunction mouse model (Ppp1r2-cre/fGluN1 KO mice), we investigated whether oxidative stress is implicated in the social isolation-induced exacerbation of schizophrenia-like phenotypes and further explored the underlying mechanism of elevated oxidative stress in KO mice. The reactive oxygen species (ROS) level in the cortex of group-housed KO mice was normal at eight weeks although increased at 16 weeks old. Post-weaning social isolation (PWSI) augmented the ROS levels in KO mice at both ages, which was accompanied by the onset of behavioral phenotype. Chronic treatment with apocynin, an ROS scavenger, abolished markers of oxidative stress and partially alleviated schizophrenia-like behavioral phenotypes in KO mice. Markers of oxidative stress following PWSI were especially prominent in cortical parvalbumin (PV)-positive interneurons. The vulnerability of PV interneurons to oxidative stress was associated with down-regulation of peroxisome proliferator-activated receptor α coactivator-13 (PGC-1α), a master regulator of mitochondrial energy metabolism and antioxidation. These results suggest that a PWSI-mediated impairment in antioxidant defense mechanisms, presumably mediated by PGC-1α downregulation in the NMDAR-deleted PV-positive interneurons, results in oxidative stress, which, in turn, may contribute to exacerbation of schizophrenia-like behavioral phenotypes.
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影响因子：
2.5
作者：
Bayer, TA;Buslei, R;Falkai, P
通讯作者：
Falkai, P
DOI：
10.1080/19485565.1973.9988053
发表时间：
1973-01-01
期刊：
SOCIAL BIOLOGY
影响因子：
--
作者：
FULKER, DW
通讯作者：
FULKER, DW
影响因子：
6.7
作者：
Brown AS
通讯作者：
Brown AS
影响因子：
4.8
作者：
Bayer, TA;Falkai, P;Maier, W
通讯作者：
Maier, W
白介素-6介导精神分裂症的氯胺酮模型中NADPH-氧化酶的增加。
DOI：
10.1523/jneurosci.4457-08.2008
发表时间：
2008-12-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Behrens MM;Ali SS;Dugan LL
通讯作者：
Dugan LL