Epigenetic modification of PKMζ rescues aging-related cognitive impairment

被引：14

作者：

Chen, Chen ^{[1
,2
,3
,4
]}

Meng, Shi-Qiu ^{[1
,2
,3
,4
]}

Xue, Yan-Xue ^{[3
,4
]}

Han, Ying ^{[3
,4
]}

Sun, Cheng-Yu ^{[1
,2
,3
,4
]}

Deng, Jia-Hui ^{[1
,2
,3
,4
]}

Chen, Na ^{[3
,4
]}

Bao, Yan-Ping ^{[3
,4
]}

Zhang, Fei-Long ^{[3
,4
]}

Cao, Lin-Lin ^{[5
]}

Zhu, Wei-Guo ^{[5
]}

Shi, Jie ^{[3
,4
]}

Song, Wei-Hong ^{[8
,9
]}

Lu, Lin ^{[1
,2
,3
,4
,6
,7
]}

机构：

[1] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing 100191, Peoples R China

[2] Key Lab Mental Hlth, Beijing 100191, Peoples R China

[3] Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China

[4] Peking Univ, Beijing Key Lab Drug Dependence Res, Beijing 100191, Peoples R China

[5] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China

[6] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[7] Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China

[8] Univ British Columbia, Dept Med, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada

[9] Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

KINASE M-ZETA; RETRIEVAL-EXTINCTION PROCEDURE; MEDIAL PREFRONTAL CORTEX; ACTIVE DNA DEMETHYLATION; DEPRESSIVE-LIKE BEHAVIOR; ENVIRONMENTAL ENRICHMENT; BASOLATERAL AMYGDALA; MEMORY FORMATION; WORKING-MEMORY; SPATIAL MEMORY;

D O I：

10.1038/srep22096

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase M zeta (PKM zeta) in the prelimbic cortex (PrL). PKM zeta is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKM zeta in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKM zeta and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKM zeta DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKM zeta DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKM zeta and restored cognitive performance in aged rats. Inactivation of PKM zeta prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKM zeta might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

引用

页数：17

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