Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence

doi:10.1097/FBP.0000000000000643

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	Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence
	Du, Wei 1; Li, Man 4,5,6; Zhou, Hao 1; Shao, Feng 1; Wang, Weiwen 2,3
刊名	BEHAVIOURAL PHARMACOLOGY
	2021-09-01
卷号	32 期号:6 页码:487-496
关键词	adolescent social isolation cAMP-dependent protein kinase A cAMP-response element-binding protein medial prefrontal cortex prepulse inhibition
ISSN号	0955-8810
DOI	10.1097/FBP.0000000000000643
通讯作者	Shao, Feng(shaof@pku.edu.cn)
英文摘要	Prepulse inhibition (PPI) refers to the inhibition of the startle reflex that occurs when the startling stimulus is preceded by a weak prestimulus. Altered adolescent mPFC circuitry induced by early-life adversity might be a key source of PPI deficits. The current study focused on variations in the cyclic AMP (cAMP)/protein kinase A (PKA)-cAMP-response element-binding protein (CREB) pathway in the medial prefrontal cortex (mPFC). We found a negative relationship between PPI and the PKA-CREB cascade during adolescence by employing both developmental and pharmacologic manipulations. Experiment 1, with the early adolescent social isolation model [postnatal days (PNDs), 21-34), displayed a disrupted PPI at PND 35 and significantly altered PKA, phosphorylated CREB (p-CREB) and the ratio of p-CREB to CREB. In particular, the level of p-CREB was negatively related to PPI performance. In Experiment 2, SKF38393, a well-characterized activator of adenylate cyclase and cAMP/PKA, was chronically injected during early adolescence (PNDs 28-34). We sought to mimic potential biochemical changes, particularly PKA activation, which is possibly altered by adolescent social isolation, and to determine if PPI was disrupted, similar to the disruption associated with adolescent social isolation. On PND 35, PPI deficits were detected, as well as increased PKA, marginally increased CREB and no change occurred in p-CREB or the ratio of p-CREB to CREB. In particular, PKA activity was negatively related to PPI performance. Although these results are limited in suggesting a causal link between PPI deficits and PKA-CREB signaling, they may help to elucidate the role played by PKA-CREB in the mPFC in regulating PPI.
收录类别	SCI
资助项目	National Natural Science Foundation of China[31470988] ; National Natural Science Foundation of China[81471122] ; Department of Psychology, Chinese Academy of Sciences[KJZD-EW-L04] ; Beijing Key Laboratory of Behavior and Mental Health, the Chinese Academy of Sciences[KJZD-EW-L04] ; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences
WOS关键词	MEDIAL PREFRONTAL CORTEX ; SENSORIMOTOR GATING DEFICITS ; ISOLATION-REARED RATS ; NUCLEUS-ACCUMBENS ; NEUROTROPHIC FACTORS ; GENE-EXPRESSION ; SCHIZOPHRENIA ; RECEPTOR ; STARTLE ; PHOSPHORYLATION
WOS研究方向	Behavioral Sciences ; Neurosciences & Neurology ; Pharmacology & Pharmacy
语种	英语
出版者	LIPPINCOTT WILLIAMS & WILKINS
WOS记录号	WOS:000683520100004
资助机构	National Natural Science Foundation of China ; Department of Psychology, Chinese Academy of Sciences ; Beijing Key Laboratory of Behavior and Mental Health, the Chinese Academy of Sciences ; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences
内容类型	期刊论文
源URL	[http://ir.psych.ac.cn/handle/311026/40007]
专题	心理研究所_中国科学院心理健康重点实验室
通讯作者	Shao, Feng
作者单位	1.Peking Univ, Sch Psychol & Cognit Sci, Beijing Key Lab Behav & Mental Hlth, 5 Yiheyuan Rd, Beijing 100871, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing, Peoples R China 4.Tianjin Social Sci Lab Students Mental Dev & Lear, Tianjin, Peoples R China 5.Tianjin Normal Univ, Fac Psychol, Tianjin, Peoples R China 6.Tianjin Normal Univ, Minist Educ, Acad Psychol & Behav, Key Res Base Humanities & Social Sci, Tianjin, Peoples R China
推荐引用方式 GB/T 7714	Du, Wei,Li, Man,Zhou, Hao,et al. Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence[J]. BEHAVIOURAL PHARMACOLOGY,2021,32(6):487-496.
APA	Du, Wei,Li, Man,Zhou, Hao,Shao, Feng,&Wang, Weiwen.(2021).Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence.BEHAVIOURAL PHARMACOLOGY,32(6),487-496.
MLA	Du, Wei,et al."Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence".BEHAVIOURAL PHARMACOLOGY 32.6(2021):487-496.