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Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats.

ABSTRACT: Excessive neuroinflammatory responses play important roles in the development of postoperative cognitive dysfunction (POCD). Neurofilaments (NFs) were essential to the structure of axon and nerve conduction; and the abnormal degradation of NFs were always accompanied with degenerative diseases, which were also characterized by excessive neuroinflammatory responses in brain. However, it is still unclear whether the NFs were involved in the POCD. In this study, the LC-MS/MS method was used to explore the neuroinflammatory response and NFs of POCD in aged rats. Moreover, trichostatin A (TSA), an inflammation-related drug, was selected to test whether it could improve the surgery-induced cognitive dysfunction, inflammatory responses and NFs. Evident cognitive dysfunction, excessive microglia activation, neuroinflammatory responses and upregulated NFs in hippocampus were observed in the POCD group. TSA pretreatment could significantly mitigate these changes. The KEGG analysis revealed that nine pathways were enriched in the TSA + surgery group (versus the surgery group). Among them, two signaling pathways were closely related with the changes of NFs proteins. In conclusion, surgery could impair the cognitive function and aggravate neuroinflammation and NFs. The TSA could significantly improve these changes which might be related to the activation of the "focal adhesion" and "ECM-receptor interaction" pathways.

SUBMITTER: Cao Y

PROVIDER: S-EPMC7803518 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats.

Cao Yiyun Y Liu Taotao T Li Zhengqian Z Yang Jiao J Ma Lijun L Mi Xinning X Yang Ning N Qi Aihua A Guo Xiangyang X Wang Aizhong A

Aging 20201124 24

Excessive neuroinflammatory responses play important roles in the development of postoperative cognitive dysfunction (POCD). Neurofilaments (NFs) were essential to the structure of axon and nerve conduction; and the abnormal degradation of NFs were always accompanied with degenerative diseases, which were also characterized by excessive neuroinflammatory responses in brain. However, it is still unclear whether the NFs were involved in the POCD. In this study, the LC-MS/MS method was used to expl ...[more]

PMID: 33232265

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Project description:BACKGROUND:This study aimed to evaluate effects of electric vagal nerve stimulation on early postoperation cognitive dysfunction in aged rats. METHODS:A total of 33 male Sprague Dawley rats were selected and assigned randomly to three groups, control group (C, n?=?10), splenectomy group (S, n?=?10) and splenectomy+vagal nerve stimulation group (SV, n?=?13). Behavior and memory of rats were evaluated by Open Field Test and Morris Water Maze. Levels of TNF-?, IL-6 and IL-10 in serum were measured by ELISA. The level of TNF-? protein in hippocampus was assessed by Western blotting. rt-PCR was used to detect mRNA expression of NF-?B in hippocampus. RESULTS:During anesthesia/operation, vital life signs of rats were stable. In SV group, vagal nerve stimulation decreased heart rate lower than 10% of basic level and kept it at a stable range by regulating stimulation intensity. After stimulation stop, heart rate returned to the basic level again. This indicated that the model of vagal nerve stimulation was successful. Serum levels of TNF-? and IL-6 increased by the operation/anesthesia, but they decreased with vagal nerve stimulation (all P?<?0.05). TNF-? protein and mRNA expression of NF-?B in hippocampus were also eliminated by vagal nerve stimulation compared to S group (P?<?0.05). Results of Morris Water Maze showed escape latency of postoperation in S group was significantly longer than C group (P?<?0.05), and times of crossing platform in S group was lower than that of C group (P?<?0.05). Although escape latency of postopration in SV group was shorter than that of S group, there was no significant difference between two groups. Meanwhile there were no significant differences of behavior test in Open Field test between three groups, although vagal nerve stimulation improved partly active explore behavior compared to S group. CONCLUSION:The inflammation caused by operation and general anesthesia was an important reason of early postoperation cognitive dysfunction, and electric vagal nerve stimulation could inhibit the inflammation. Meanwhile, vagal nerve stimulation could ameliorate early postoperation cognitive dysfunction partly, but its protective effects were not enough and should be studied and improved in future.

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Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats.

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Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats.

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