title: Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation.
abstract: Astrocytes are proving to be critical for the development of cognitive functions. In addition, astrocytic activation contributes to cognitive impairment induced by chronic cerebral hypoperfusion. Minocycline has been shown to exhibit long-term neuroprotective effects in vascular cognitive impairment rat models through the inhibition of astrogliosis, and has demonstrated potential for the prevention and treatment of postoperative cognitive decline in elderly patients. This study aimed to examine the effect of minocycline on hippocampal astrocytes and long-term postoperative cognitive dysfunction in aged mice. Mice were intraperitoneally injected with 45 mg/kg minocycline once a day for 30 days after 70% hepatectomy. Hippocampus-dependent spatial memory ability was evaluated using the Morris water maze test. The expression levels of hippocampal glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 were evaluated by western blotting, and the hippocampal mRNA relative expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were tested using real-time PCR. The Morris water maze test showed that escape latency and swim distance were significantly prolonged by the surgery, but the extent of impairment was mitigated by minocycline treatment. Hippocampal GFAP levels and mRNA levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 showed corresponding changes that were consistent with the variations in spatial memory. Minocycline was able to alleviate hepatectomy-related long-term spatial memory impairment in aged mice, and was associated with reduced levels of hippocampal GFAP and proinflammatory cytokines resulting from astrocytic activation.
authors.affiliation: aDepartment of Anesthesiology, The First Affiliated Hospital (Jiangsu Province Hospital), Nanjing Medical University bState Key Laboratory of Reproductive Medicine, Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Jin
authors.forename: Shan-Wu
authors.initials: SW
authors.lastname: Feng
authors.forename: Zhou
authors.initials: Z
authors.lastname: Feng
authors.forename: Shun-Mei
authors.initials: SM
authors.lastname: Lu
authors.forename: Tao
authors.initials: T
authors.lastname: Qi
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Qian
mesh_terms: D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006498:Hepatectomy / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D008911:Minocycline