Imagine your brain is a complex machine like a car. As you get older, the engine starts to wear down, just like your brain. Scientists have discovered that aging and neurodegenerative diseases like Alzheimer’s affect the mitochondria (the powerhouses of the cell) and the synapses (connections between brain cells). But what about when it comes to memory problems after surgery? Well, it turns out that surgery can make these brain problems even worse! In this study, researchers used special mazes to test the memory of mice at different ages. They found that both aging and surgery caused cognitive impairment, mitochondrial dysfunction, and problems with a process called autophagy (which is like the brain’s garbage disposal system). The good news is that they also discovered two proteins called PKC and PKR that play a role in these brain problems. By blocking these proteins, they were able to improve cognitive function, mitochondrial health, and autophagy in mice. So, if we can find ways to target PKC and PKR, we might be able to treat or prevent age-related cognitive decline and neurodegenerative diseases like Alzheimer’s. It’s an exciting area of research that could have big implications for our brain health!

BackgroundThe incidence of perioperative neurocognitive disorders (PNDs) is reportedly higher in older patients. Mitochondrial and synaptic dysfunctions have consistently been demonstrated in models of aging and neurodegenerative diseases; nonetheless, their role in PND is not well understood.MethodsThe Morris water maze and elevated plus maze tests were used to assess the learning and memory abilities of both C57BL/6 and 3×Tg-AD mice of different ages (8 and 18 months). PND was induced by laparotomy in C57BL/6 mice and 3×Tg-AD mice (8 months old). Markers associated with neuroinflammation, mitochondrial function, synaptic function, and autophagy were assessed postoperatively. The roles of protein kinase C (PKC) and double-stranded RNA-dependent protein kinase (PKR) were further demonstrated by using PKC-sensitive inhibitor bisindolylmaleimide X (BIMX) or PKR−/− mice.ResultsSignificant cognitive impairment was accompanied by mitochondrial dysfunction and autophagy inactivation in both aged C57BL/6 and 3×Tg-AD mice. Laparotomy induced a significant neuroinflammatory response and synaptic protein loss in the hippocampus. Cognitive and neuropathological changes induced by aging or laparotomy were further exacerbated in 3×Tg-AD mice. Deficits in postoperative cognition, hippocampal mitochondria, autophagy, and synapse were significantly attenuated after pharmacological inhibition of PKC or genetic deletion of PKR.ConclusionsOur findings suggest similar pathogenic features in aging, Alzheimer’s disease, and PND, including altered mitochondrial homeostasis and autophagy dysregulation. In addition, laparotomy may exacerbate cognitive deficits associated with distinct neuronal inflammation, mitochondrial dysfunction, and neuronal loss independent of genetic background. The dysregulation of PKC/PKR activity may participate in the pathogenesis of these neurodegenerative diseases.

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