Loss of the neuronal genome organizer and transcription factorCTCFinduces neuronal death and reactive gliosis in the anterior cingulate cortex

초록

CCCTC-binding factor (CTCF) is a genome organizer that regulates gene expression through transcription and chromatin structure regulation. CTCF also plays an important role during the developmental and adult stages. Cell-specific CTCF deletion studies have shown that a reduction in CTCF expression leads to the development of distinct clinical features and cognitive disorders. Therefore, we knocked outCtcf(CTCFcKO) in the excitatory neurons of the forebrain in aCamk2a-Cremouse strain to examine the role of CTCF in cell death and gliosis in the cortex.CTCFcKO mice were viable, but they demonstrated an age-dependent increase in reactive gliosis of astrocytes and microglia in the anterior cingulate cortex (ACC) from 16 weeks of age prior to neuronal loss observed at over 20 weeks of age. Consistent with these data, qRT-PCR analysis of theCTCFcKO ACC revealed changes in the expression of inflammation-related genes (Hspa1a,Prokr2andItga8) linked to gliosis and neuronal death. Our results suggest that prolongedCtcfgene deficiency in excitatory neurons results in neuronal cell death and gliosis, possibly through functional changes in inflammation-related genes.

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