Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice

Area of Science:

• Neuroscience
• Gerontology
• Molecular Biology

Background:

• Postoperative cognitive dysfunction (POCD) is a significant clinical challenge with unclear neuropathogenesis and unestablished interventions.
• The role of sex-determining region Y-box-2 (Sox2), regulated by sirtuin 1, in POCD remains to be elucidated.

Purpose of the Study:

• To investigate if environmental enrichment (EE) or cognitive enrichment (CE) can mitigate POCD in aged male mice.
• To determine the involvement of Sox2, modulated by sirtuin 1, in the protective effects of EE and CE against POCD.

Main Methods:

• Aged male mice underwent a surgical procedure simulating carotid artery exposure under sevoflurane anesthesia.
• Mice received EE or CE post-surgery, with learning and memory assessed using the Barnes maze and fear conditioning.
• Sox2 expression was quantified via immunofluorescence, and its role was further examined by silencing it using small hairpin RNA (shRNA).

Main Results:

• Surgery led to a significant reduction in hippocampal Sox2-positive cells and impaired learning and memory.
• Both EE and CE attenuated the decrease in Sox2 cells and ameliorated POCD.
• Sirtuin 1 activity was reduced by surgery, an effect mitigated by CE. Resveratrol, a sirtuin 1 activator, also reduced POCD and Sox2 cell decrease.
• Silencing Sox2 independently impaired learning and memory in non-surgical mice.

Conclusions:

• Sox2 plays a crucial role in learning, memory, and the development of POCD.
• EE and CE effectively attenuate POCD by preserving Sox2-positive cells in the hippocampus, suggesting a novel therapeutic avenue.