Cerebral cortex
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Oligodendrocyte genes and white matter tracts have been implicated in the pathophysiology of schizophrenia and may play an important etiopathogenic role in cognitive dysfunction in schizophrenia. The objective of the present study in 60 chronic schizophrenia patients individually matched to 60 healthy controls was to determine whether 1) white matter tract integrity influences cognitive performance, 2) oligodendrocyte gene variants influence white matter tract integrity and cognitive performance, and 3) effects of oligodendrocyte gene variants on cognitive performance are mediated via white matter tract integrity. We used the partial least-squares multivariate approach to ascertain relationships among oligodendrocyte gene variants, integrity of cortico-cortical and subcortico-cortical white matter tracts, and cognitive performance. ⋯ We also showed that effects of gene variants on cognitive performance were mediated by the integrity of white matter tracts. Our results were strengthened by bioinformatic analyses of gene variant function. To our knowledge, this is the first study that has brought together these lines of investigation in the same population and highlights the importance of the oligodendrocyte/white matter pathway in schizophrenia, particularly as it pertains to cognitive function.
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The rostral anterior cingulate cortex (rACC) is a key structure of pain affect. Whether and how estrogen in the rACC regulates pain-related negative emotion remains unclear. Behaviorally, using formalin-induced conditioned place aversion (F-CPA) in rats, which is believed to reflect the pain-related negative emotion, we found that estrogen receptor (ER) inhibitor ICI 182, 780 (ICI, 7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol) or inhibitor of aromatase androstatrienedione into the rACC completely blocked F-CPA in either sex. ⋯ Interestingly, a brief exposure to estrogen elicited a persistent enhancement of NMDA-EPSCs, and this NMDA-long-term potentiation required the activation of the mERs, protein kinase A and NMDAR subunit NR2B. Finally, estrogen induced rapid dendritic spine formation in cultured rACC neurons. These results suggest that estrogen in the rACC, as a neuromodulator, drives affective pain via facilitating NMDA receptor-mediated synaptic transmission.