Journal of neurochemistry
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Journal of neurochemistry · Sep 2012
Harnessing pain heterogeneity and RNA transcriptome to identify blood-based pain biomarkers: a novel correlational study design and bioinformatics approach in a graded chronic constriction injury model.
A quantitative, peripherally accessible biomarker for neuropathic pain has great potential to improve clinical outcomes. Based on the premise that peripheral and central immunity contribute to neuropathic pain mechanisms, we hypothesized that biomarkers could be identified from the whole blood of adult male rats, by integrating graded chronic constriction injury (CCI), ipsilateral lumbar dorsal quadrant (iLDQ) and whole blood transcriptomes, and pathway analysis with pain behavior. Correlational bioinformatics identified a range of putative biomarker genes for allodynia intensity, many encoding for proteins with a recognized role in immune/nociceptive mechanisms. ⋯ This study is the first to employ the whole blood transcriptome to identify pain biomarker panels. The novel correlational bioinformatics, developed here, selected such putative biomarkers based on a correlation with pain behavior and formation of signaling pathways with iLDQ genes. Future studies may demonstrate the predictive ability of these biomarker genes across other models and additional variables.
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Journal of neurochemistry · Sep 2012
Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons.
Urocortin 3 (also known as stresscopin) is an endogenous ligand for the corticotropin-releasing factor receptor 2 (CRF(2)). Despite predominant G(s) coupling of CRF(2), promiscuous coupling with other G proteins has been also associated with the activation of this receptor. As urocortin 3 has been involved in central cardiovascular regulation at hypothalamic and medullary sites, we examined its cellular effects on cardiac vagal neurons of nucleus ambiguus, a key area for the autonomic control of heart rate. ⋯ Urocortin 3 activated Ca(2+) influx via voltage-gated P/Q-type channels as well as Ca(2+) release from endoplasmic reticulum. Urocortin 3 promoted Ca(2+) release via inositol 1,4,5 trisphosphate receptors, but not ryanodine receptors. Our results indicate a novel Ca(2+) -mobilizing effect of urocortin 3 in vagal pre-ganglionic neurons of nucleus ambiguus, providing a cellular mechanism for a previously reported role for this peptide in parasympathetic cardiac regulation.
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Journal of neurochemistry · Sep 2012
Thermal sensitivity of voltage-gated Na+ channels and A-type K+ channels contributes to somatosensory neuron excitability at cooling temperatures.
Cooling temperatures may modify action potential firing properties to alter sensory modalities. Herein, we investigated how cooling temperatures modify action potential firing properties in two groups of rat dorsal root ganglion (DRG) neurons, tetrodotoxin-sensitive (TTXs) Na(+) channel-expressing neurons and tetrodotoxin-resistant (TTXr) Na(+) channel-expressing neurons. ⋯ We demonstrated that the sensitivity of A-type K(+) channels and voltage-gated Na(+) channels to cooling temperatures and their interplay determine somatosensory neuron excitability at cooling temperatures. Our results provide a putative mechanism by which cooling temperatures modify different sensory modalities including pain.
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Journal of neurochemistry · Aug 2012
MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors.
Parkinson's disease (PD)-like symptoms and cognitive deficits are inducible by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Since cognitive abilities, including memory formations rely also on hippocampus, we set out to clarify the effects of MPTP on hippocampal physiology. We show that bath-application of MPTP (25 μM) to acute hippocampal slices enhanced AMPA receptor-mediated field excitatory postsynaptic potentials (AMPAr-fEPSPs) transiently, whereas N-methyl-D-aspartate (NMDA) receptor-mediated fEPSPs (NMDAr-fEPSPs) were facilitated persistently. ⋯ Regarding activity-dependent synaptic plasticity, 25 μM MPTP transformed short-term potentiation (STP) into a long-term potentiation (LTP) and caused a slow onset potentiation of a non-tetanized synaptic input after induction of LTP in a second synaptic input. This heterosynaptic slow onset potentiation required activation of dopamine D1-like and NMDA-receptors. We conclude that acute MPTP application affects basal synaptic transmission by modulation of presynaptic vesicle release and facilitates NMDAr-fEPSPs as well as activity-dependent homo- and heterosynaptic plasticity under participation of dopamine receptors.
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Journal of neurochemistry · Aug 2012
7,8-dihydroxyflavone rescues spatial memory and synaptic plasticity in cognitively impaired aged rats.
7,8-dihydroxyflavone (7,8-DHF) has recently been identified as a potential TrkB agonist that crosses the blood-brain barrier after i.p. administration. We previously demonstrated that 7,8-DHF in vitro rescues long-term synaptic plasticity in the hippocampus of aged rats. This study assessed the rescue effect of 7,8-DHF in vivo on aging-related cognitive impairment in rats, and further determined whether the effect of 7,8-DHF is age dependent. ⋯ Taken together, our results suggest that 7,8-DHF can act in vivo to counteract aging-induced declines in spatial memory and synaptic plasticity and morphological changes of hippocampal neurons. The effect of 7,8-DHF is more pronounced in relatively younger impaired rats than in those of more advanced age. These findings demonstrate the reversal of age-dependent memory impairment by in vivo 7,8-DHF application and support the benefit of early treatment for cognitive aging.