Dysfunction of mitochondria and GABAergic interneurons in the anterior cingulate cortex of individuals with schizophrenia

被引:4
作者
Kondo, Mari A. [2 ]
Norris, Alexis L. [1 ,2 ,3 ]
Yang, Kun [2 ]
Cheshire, Madeline [1 ]
Newkirk, Isabelle [1 ]
Chen, Xiangning [4 ,5 ]
Ishizuka, Koko [2 ]
Jaffe, Andrew E. [6 ,7 ]
Sawa, Akira [2 ,3 ,7 ,8 ,9 ,10 ]
Pevsner, Jonathan [1 ,2 ,3 ]
机构
[1] Kennedy Krieger Inst, Dept Neurol, Baltimore, MD USA
[2] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA
[3] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA
[4] Univ Nevada, Nevada Inst Personalized Med, Dept Psychol, United States Amer, Las Vegas, NV USA
[5] Univ Nevada, Dept Psychol, Las Vegas, NV USA
[6] Lieber Inst Brain Dev, Johns Hopkins Med Campus, Baltimore, MD USA
[7] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA
[8] Johns Hopkins Sch Med, Dept Biomed Engn, Baltimore, MD USA
[9] Johns Hopkins Sch Med, Dept Genet Med, Baltimore, MD USA
[10] Johns Hopkins Sch Med, Dept Pharmacol, 6001 Execut Blvd, Baltimore, MD 20852 USA
关键词
Schizophrenia; Gene expression; Quality surrogate variable analysis; Anterior cingulate cortex; Redox imbalance; Mitochondrial dysfunction; GENE-ENVIRONMENT INTERACTIONS; EXPRESSION ANALYSIS; PREFRONTAL CORTEX; OXIDATIVE STRESS; MODELS; ASSOCIATION; DIVERSITY;
D O I
10.1016/j.neures.2022.09.011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Here we re-analyze RNA-sequencing data from the anterior cingulate cortex (ACC) of SZ patients using recent methods to improve accuracy and sensitivity of results, such as the quality surrogate variable analysis (qSVA) method and the derfinder R package. We found that genes significantly down-regulated in SZ demonstrated an enrichment for parvalbumin-positive interneurons (FDR < 0.0001). Down-regulated genes were also enriched in oxidative phosphorylation functions (FDR < 0.05). We also addressed whether lifetime exposure to antipsy-chotics might influence gene expression, highlighting DUSP6, LBH, and NR1D1. Our results support the role of redox imbalance/mitochondrial dysfunction and implicate interneuron subtypes in SZ pathophysiology.
引用
收藏
页码:67 / 72
页数:6
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