Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline.
Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline.
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DOI：
10.1172/jci.insight.166175
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发表时间：
2023-05-22
期刊：
影响因子：
8
通讯作者：
Du, Heng
中科院分区：
文献类型：
--
作者：
Tian, Jing;Guo, Lan;Wang, Tienju;Jia, Kun;Swerdlow, Russell H.;Zigman, Jeffrey M.;Du, Heng
Elderly individuals frequently report cognitive decline, while various studies indicate hippocampal functional declines with advancing age. Hippocampal function is influenced by ghrelin through hippocampus-expressed growth hormone secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous GHSR antagonist that attenuates ghrelin signaling. Here, we measured plasma ghrelin and LEAP2 levels in a cohort of cognitively normal individuals older than 60 and found that LEAP2 increased with age while ghrelin (also referred to in literature as “acyl-ghrelin”) marginally declined. In this cohort, plasma LEAP2/ghrelin molar ratios were inversely associated with Mini-Mental State Examination scores. Studies in mice showed an age-dependent inverse relationship between plasma LEAP2/ghrelin molar ratio and hippocampal lesions. In aged mice, restoration of the LEAP2/ghrelin balance to youth-associated levels with lentiviral shRNA Leap2 downregulation improved cognitive performance and mitigated various age-related hippocampal deficiencies such as CA1 region synaptic loss, declines in neurogenesis, and neuroinflammation. Our data collectively suggest that LEAP2/ghrelin molar ratio elevation may adversely affect hippocampal function and, consequently, cognitive performance; thus, it may serve as a biomarker of age-related cognitive decline. Moreover, targeting LEAP2 and ghrelin in a manner that lowers the plasma LEAP2/ghrelin molar ratio could benefit cognitive performance in elderly individuals for rejuvenation of memory.
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影响因子：
5.8
作者：
Fittipaldi, Antonela S.;Hernandez, Julieta;Perello, Mario
通讯作者：
Perello, Mario
DOI：
10.1016/s0169-328x(97)00071-5
发表时间：
1997-08-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Guan, XM;Yu, H;Howard, AD
通讯作者：
Howard, AD
影响因子：
3.3
作者：
Harada CN;Natelson Love MC;Triebel KL
通讯作者：
Triebel KL
影响因子：
20.1
作者：
Chia CW;Egan JM;Ferrucci L
通讯作者：
Ferrucci L
影响因子：
5.6
作者：
Amitani M;Amitani H;Cheng KC;Kairupan TS;Sameshima N;Shimoshikiryo I;Mizuma K;Rokot NT;Nerome Y;Owaki T;Asakawa A;Inui A
通讯作者：
Inui A