Research Paper Volume 12, Issue 24 pp 25643—25657
Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats
- 1 Department of Anesthesiology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China
- 2 Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China
- 3 Department of Pharmacy, Sixth People’s Hospital East Campus Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China
- 4 Department of Medical Imaging, North Minzu University, Yinchuan, Ningxia 750021, China
Received: April 21, 2020 Accepted: September 19, 2020 Published: November 24, 2020https://doi.org/10.18632/aging.104172
How to Cite
Copyright: © 2020 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
POCD: postoperative cognitive dysfunction; TSA: Trichostatin A; NFs: neurofilaments; NEFL: neurofilament light chain; NEFM: neurofilament medium chain; NEFH: neurofilament heavy chain; BBB: blood brain barrier; IL-1β: interleukin-1β; TNF-α: tumor necrosis factor-alpha; HDAC: histone deacetylase; ECM: extracellular matrix; MWM: Morris water maze; iTRAQ: isobaric tags for relative and absolute quantitation; KEGG: Kyoto Encyclopedia of Genes and Genomes; NanoLC-MS/MS: nano liquid chromatography-mass spectrometry.