Histone Deacetylase Inhibitor MS-275 Alleviates Postoperative Cognitive Dysfunction in Rats by Inhibiting Hippocampal...

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Neuroinflammation in the hippocampus is crucial for postoperative cognitive dysfunction (POCD).
• Histone deacetylases (HDACs) regulate neuroinflammation, and MS-275 is an HDAC inhibitor with potential neuroprotective effects.

Purpose of the Study:

• To investigate if MS-275 pretreatment prevents POCD by inhibiting neuroinflammation in a rat model.
• To evaluate the effects of MS-275 on cognitive function, microglial activation, and inflammatory markers in the hippocampus.

Main Methods:

• Rats underwent anesthesia/surgery, followed by cognitive assessment using the Morris water maze (MWM).
• Hippocampal tissues were analyzed for microglia activation, PSD-95 expression, NF-κB-p65, pro-inflammatory cytokines (TNF-α, IL-1β), HDAC2 expression, and HDAC activity.
• MS-275 was administered as a pretreatment before anesthesia/surgery.

Main Results:

• Anesthesia/surgery impaired cognition, increased microglial activation, decreased PSD-95, and elevated NF-κB-p65 and pro-inflammatory cytokines.
• MS-275 pretreatment attenuated cognitive impairment, reduced microglial activation, and increased PSD-95 expression.
• MS-275 decreased NF-κB-p65 nuclear accumulation, pro-inflammatory cytokine production, and also reduced HDAC2 expression and activity.

Conclusions:

• MS-275 alleviates POCD in rats by inhibiting hippocampal neuroinflammation.
• The mechanism involves reducing microglial activation, pro-inflammatory cytokine production, and modulating HDAC activity.
• MS-275 demonstrates potential as a therapeutic agent for preventing POCD.