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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, Wei1; Li, Man2,3,4; Zhou, Hao1; Shao, Feng1; Wang, Weiwen5,6 | |
第一作者 | Wei Du |
通讯作者邮箱 | shaof@pku.edu.cn (feng shao) |
心理所单位排序 | 5 |
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. |
关键词 | adolescent social isolation cAMP-dependent protein kinase A cAMP-response element-binding protein medial prefrontal cortex prepulse inhibition |
2021-09-01 | |
语种 | 英语 |
DOI | 10.1097/FBP.0000000000000643 |
发表期刊 | BEHAVIOURAL PHARMACOLOGY |
ISSN | 0955-8810 |
卷号 | 32期号:6页码:487-496 |
期刊论文类型 | 实证研究 |
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 |
出版者 | LIPPINCOTT WILLIAMS & WILKINS |
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 |
WOS类目 | Behavioral Sciences ; Neurosciences ; Pharmacology & Pharmacy |
WOS记录号 | WOS:000683520100004 |
WOS分区 | Q3 |
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 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.psych.ac.cn/handle/311026/40008 |
专题 | 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.Tianjin Normal Univ, Minist Educ, Acad Psychol & Behav, Key Res Base Humanities & Social Sci, Tianjin, Peoples R China 3.Tianjin Normal Univ, Fac Psychol, Tianjin, Peoples R China 4.Tianjin Social Sci Lab Students Mental Dev & Lear, Tianjin, Peoples R China 5.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing, Peoples R China 6.Univ Chinese Acad Sci, Beijing, 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. |
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