Open AccessCholecystokinin octapeptide improves hippocampal glutamatergic synaptogenesis and postoperative cognition by inhibiting induction of A1 reactive astrocytes in aged mice
Author(s) -
Chen Lei,
Yang Ning,
Li Yue,
Li Yitong,
Hong Jingshu,
Wang Qian,
Liu Kaixi,
Han Dengyang,
Han Yongzheng,
Mi Xinning,
Shi Chengmei,
Zhou Ying,
Li Zhengqian,
Liu Taotao,
Guo Xiangyang
Publication year - 2021
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13718
Subject(s) - glutamatergic , synaptogenesis , microglia , hippocampus , cholecystokinin , morris water navigation task , neuroscience , hippocampal formation , glutamate receptor , medicine , psychology , inflammation , receptor
Aims Delayed neurocognitive recovery (dNCR) is a common postoperative complication in geriatric surgical patients for which there is no efficacious therapy. Cholecystokinin octapeptide (CCK‐8), an immunomodulatory peptide, regulates memory and learning. Here, we explored the effects and mechanism of action of CCK‐8 on dNCR. Methods We applied laparotomy to establish a model of dNCR in aged mice. Morris water maze and fear conditioning tests were used to evaluate cognition. Immunofluorescence was used to detect the density of CCK‐8, A1 reactive astrocytes, glutamatergic synapses, and activation of microglia in the hippocampus. Quantitative PCR was performed to determine mRNA levels of synapse‐associated factors. A1 reactive astrocytes, activated microglia, and glutamatergic synapse‐associated protein levels in the hippocampus were assessed by western blotting. Results Administration of CCK‐8 suppressed the activation of microglia, the induction of A1 reactive astrocytes, and the expression of tumor necrosis factor alpha, complement 1q, and interleukin 1 alpha in the hippocampus. Furthermore, it promoted glutamatergic synaptogenesis and neurocognitive recovery in aged dNCR model mice. Conclusion Our findings indicated that CCK‐8 alleviated cognitive impairment and promoted glutamatergic synaptogenesis by inhibiting the induction of A1 reactive astrocytes and the activation of microglia. CCK‐8 is, therefore, a potential therapeutic target for dNCR.