Journal of neurochemistry
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Journal of neurochemistry · May 2009
Delayed cerebral oxidative glucose metabolism after traumatic brain injury in young rats.
Traumatic brain injury (TBI) results in a cerebral metabolic crisis that contributes to poor neurologic outcome. The aim of this study was to characterize changes in oxidative glucose metabolism in early periods after injury in the brains of immature animals. At 5 h after controlled cortical impact TBI or sham surgery to the left cortex, 21-22 day old rats were injected intraperitoneally with [1,6-13C]glucose and brains removed 15, 30 and 60 min later and studied by ex vivo 13C-NMR spectroscopy. ⋯ Our findings indicate that (i) neuronal-specific oxidative metabolism of glucose at 5-6 h after TBI is delayed in both injured and contralateral sides compared with sham brain; (ii) labeling from metabolism of glucose via the pyruvate carboxylase pathway in astrocytes was also initially delayed in both sides of TBI brain compared with sham brain; (iii) despite this delayed incorporation, at 6 h after TBI, both sides of the brain showed apparent increased neuronal and glial metabolism, reflecting accumulation of labeled metabolites, suggesting impaired malate aspartate shuttle activity. The presence of delayed metabolism, followed by accumulation of labeled compounds is evidence of severe alterations in homeostasis that could impair mitochondrial metabolism in both ipsilateral and contralateral sides of brain after TBI. However, ongoing oxidative metabolism in mitochondria in injured brain suggests that there is a window of opportunity for therapeutic intervention up to at least 6 h after injury.
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Journal of neurochemistry · May 2009
Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure.
Pre-synaptic nerve terminals (synaptosomes) require ATP for neurotransmitter exocytosis and recovery and for ionic homeostasis, and are consequently abundantly furnished with mitochondria. Pre-synaptic mitochondrial dysfunction is implicated in a variety of neurodegenerative disorders, although there is no precise definition of the term 'dysfunction'. ⋯ We combine two novel techniques, firstly using a modification of a plate-based respiration and glycolysis assay that requires only microgram quantities of synaptosomal protein, and secondly developing an improved method for fluorescent imaging and statistical analysis of single synaptosomes. Conditions are defined for optimal substrate supply to the in situ mitochondria within mouse cerebrocortical synaptosomes, and the energetic demands of ion cycling and action-potential firing at the plasma membrane are additionally determined.
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Journal of neurochemistry · May 2009
A functional link between T-type calcium channels and mu-opioid receptor expression in adult primary sensory neurons.
The mu-opioid receptor agonists have a preferential effect on nociception in adults but their analgesic effect is less selective in neonates. Here we presented our finding that the mu-opioid receptor agonists had no effect on high voltage-activated Ca(2+) channels (HVACCs) in adult dorsal root ganglion (DRG) neurons that exhibited a prominent T-type Ca(2+) current. We also determined the mechanisms underlying the mu-opioid agonists' lack of effect on HVACCs in these neurons. ⋯ The mu-opioid receptor mRNA was detected in all neurons without T-type Ca(2+) currents and also in 28.6% of neurons with T-type Ca(2+) currents in the neonatal DRG. Our study provides novel information that adult DRG neurons with prominent T-type Ca(2+) currents do not express mu-opioid receptors. Expression of T-type Ca(2+) (Ca(V)3.2) channels and mu-opioid receptors may be developmentally co-regulated as some DRG neurons differentiate toward becoming nociceptive neurons.