DCC in the cerebral cortex is required for cognitive functions in mouse

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	DCC in the cerebral cortex is required for cognitive functions in mouse
	Hu, YQ; Liu, WT; Wu, Y; Hu, ZB; Tao, YC; Zhang, Q; Chen, JY; Li, M; Hu, L; Ding, YQ
	2024
发表期刊	BRAIN PATHOLOGY
ISSN	1015-6305
摘要	Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between deleted in colorectal cancer (DCC) and SZ. Previous study has shown a lowered expression of DCC in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of DCC statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of DCC in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI). Critically, the defective sensorimotor gating could be restored by olanzapine, an antipsychotic drug. Furthermore, we found that the levels of p-AKT and p-GSK3 alpha/beta were decreased, which was responsible for impaired PPI in the DCC-deficient mice. Finally, the DCC-deficient mice also displayed reduced spine density of pyramidal neurons and disturbed delta-oscillations. Our data, for the first time, identified and explored downstream substrates and signaling pathway of DCC which supports the hypothesis that DCC is a SZ-related risky gene and when defective, may promote SZ-like pathogenesis and behavioral phenotypes in mice.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14509
专题	科研部门_转化基因组（李明）
推荐引用方式 GB/T 7714	Hu, YQ,Liu, WT,Wu, Y,et al. DCC in the cerebral cortex is required for cognitive functions in mouse[J]. BRAIN PATHOLOGY,2024.
APA	Hu, YQ.,Liu, WT.,Wu, Y.,Hu, ZB.,Tao, YC.,...&Ding, YQ.(2024).DCC in the cerebral cortex is required for cognitive functions in mouse.BRAIN PATHOLOGY.
MLA	Hu, YQ,et al."DCC in the cerebral cortex is required for cognitive functions in mouse".BRAIN PATHOLOGY (2024).

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