Unlocking the Brain’s Defense: SIRT1 Activation Reduces Cognitive Decline After Surgery

Published on November 10, 2022

The brain is the hero of our neurologic adventure, constantly battling enemies like cognitive decline. One particular foe, known as postoperative cognitive dysfunction (POCD), can arise after surgery. Scientists have been investigating the role of microglia, the brain’s immune cells, in this ailment. But what about the changes happening on the other side of the battlefield – the synapses? A recent study dives into the action, finding that activating a powerful ally called SIRT1 can come to the rescue. Just like a secret weapon, SIRT1’s enhanced function showed reduced microglial activity, less synaptic engulfing, and improved cognitive performance in mice with POCD. These findings suggest that boosting SIRT1 could be a promising strategy to safeguard against cognitive decline after surgery. So, join the exploration and discover how SIRT1 activation unlocks the brain’s defense mechanisms! Read more about this exciting research in the link provided.

BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.

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