Journal of neurochemistry
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Journal of neurochemistry · Oct 2011
Kynurenine metabolism predicts cognitive function in patients following cardiac bypass and thoracic surgery.
Cardiac surgery involving extra-corporeal circulation can lead to cognitive dysfunction. As such surgery is associated with signs of inflammation and pro-inflammatory mediators activate tryptophan oxidation to neuroactive kynurenines which modulate NMDA receptor function and oxidative stress, we have measured blood concentrations of kynurenines and inflammatory markers in 28 patients undergoing coronary arterial graft surgery and, for comparison, 28 patients undergoing non-bypass thoracic surgery. A battery of cognitive tests was completed before and after the operations. ⋯ Changes of neopterin levels were greater after non-bypass surgery. Cognitive testing showed that the levels of tryptophan, kynurenine, kynurenic acid and the kynurenine/tryptophan ratio, correlated with aspects of post-surgery cognitive function, and were significant predictors of cognitive performance in tasks sensitive to frontal executive function and memory. Thus, anaesthesia and major surgery are associated with inflammatory changes and alterations in tryptophan oxidative metabolism which predict, and may play a role in, post-surgical cognitive function.
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Journal of neurochemistry · Oct 2011
Hidden prenatal malnutrition in the rat: role of β₁-adrenoceptors on synaptic plasticity in the frontal cortex.
Moderate reduction in the protein content of the mother's diet (hidden malnutrition) does not alter body and brain weights of rat pups at birth, but leads to dysfunction of neocortical noradrenaline systems together with impaired long-term potentiation and visuo-spatial memory performance. As β₁-adrenoceptors and downstream protein kinase signaling are critically involved in synaptic long-term potentiation and memory formation, we evaluated the β₁-adrenoceptor density and the expression of cyclic-AMP dependent protein kinase, calcium/calmodulin-dependent protein kinase and protein kinase Fyn, in the frontal cortex of prenatally malnourished adult rats. ⋯ Administration of the selective β₁ agonist dobutamine prior to tetanization completely rescued the ability of the prefrontal cortex to develop and maintain long-term potentiation in the malnourished rats. Results suggest that under-expression of neocortical β₁-adrenoceptors and protein kinase signaling in hidden malnourished rats functionally affects the synaptic networks subserving prefrontal cortex long-term potentiation. β₁-adrenoceptor activation was sufficient to fully recover neocortical plasticity in the PKA- and calcium/calmodulin-dependent protein kinase II-deficient undernourished rats, possibly by producing extra amounts of cAMP and/or by recruiting alternative signaling cascades.