Neuroscience
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Brief ( approximately 2 day) constant light exposure (LL(b)) in hamsters dramatically enhances circadian phase-resetting induced by the 5-HT receptor agonist, (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) and other nonphotic stimuli. The present study was undertaken to determine if LL(b) can also amplify phase-resetting responses to endogenous 5-HT and accelerate re-entrainment to large-magnitude advance and delay shifts of the light/dark (LD) cycle. First, central serotonergic activity was increased by i.p. injection of L-tryptophan+/-the 5-HT reuptake inhibitor fluoxetine. ⋯ In groups exposed to LL(b), vehicle controls re-entrained slowly to the advance and delay shifts (means=15+/-2 and 25+/-3 days, respectively); however those receiving 8-OH-DPAT rapidly re-entrained to the delay and advance shifts, with the majority (75%) requiring only 1-2 days (means=2+/-1 and 4+/-2 days, respectively; both P<0.05 vs. vehicle). Animals exposed to LL(b) and treated with L-tryptophan+fluoxetine also exhibited accelerated re-entrainment to a 10 h advance shift (mean=5+/-2 days; P<0.05 vs. vehicle). Thus through enhancing serotonergic phase-resetting, LL(b) facilitates rapid re-entrainment to large shifts of the LD cycle which offers a potential approach for treating circadian-related desynchronies.
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Many patients with trigeminal neuropathies suffer severe chronic pain which is inadequately alleviated with centrally-acting drugs. These drugs also possess severe side effects making compliance difficult. One strategy is to develop new treatments without central side effects by targeting peripheral sensory neurons, since sensory neuron excitability and neurotransmitter release increase in chronic pain states. ⋯ IoNC also produced long-lasting ipsilateral tactile allodynia, measured as large decreases of withdrawal thresholds to mechanical stimulation. Intradermal injection of BoNT/A in the area of infraorbital branch of the trigeminal nerve (IoN) innervation alleviated IoNC-induced mechanical allodynia and reduced the exaggerated FM4-64 release in TRG neurons from these rats. Our results suggest that BoNT/A decreases neuropathic pain behaviors by decreasing the exaggerated neurotransmitter release from TRG sensory neurons.
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Flavonoid-rich foods have been shown to be effective at reversing age-related deficits in learning and memory in both animals and humans. However, little investigation of the preventative effects of flavonoids on the naturally aged animals was reported. In our study, 14-month-old female C57BL/6 J mice were orally administered 0.025%, 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months; we found that a supplementation with 0.05% or 0.1% GTC prevented age-related spatial learning and memory decline of mice in the Morris water maze. ⋯ The expressions of brain-derived neurotrophic factor (BDNF) and Bcl-2, two target genes of CREB which can exhibit long-term regulatory roles in synaptic plasticity and synaptic structure, were also increased. We also found that long-term 0.05% or 0.1% GTC administration prevented age-related reductions of two representative post-synaptic density proteins PSD95 and Ca(2+)/calmodulin-dependent protein kinase II, suggesting that synaptic structural changes may be involved. These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent age-related spatial learning and memory decline of female C57BL/6 J mice by regulating hippocampal CREB signaling cascade.
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The posterior hypothalamus (PH) is known to reduce nociceptive pain, but the effect of PH stimulation on neuropathic pain is not known. Because neurons containing the neurotransmitter orexin-A are located in the PH in some strains of rat and intrathecal injection of orexin-A produces antinociception in a neuropathic pain model, we hypothesized that orexin-A from neurons in the PH modifies nociception in the spinal cord dorsal horn. To test this hypothesis, the cholinergic agonist carbachol or normal saline was microinjected into the PH of lightly anesthetized female Sprague-Dawley rats with chronic constriction injury (CCI) and foot withdrawal latencies (FWL) were measured. ⋯ To investigate the role of orexin-A in PH-induced antinociception, the orexin-1 receptor antagonist SB-334867 or dimethyl sulfoxide (DMSO) for control, was given intrathecally following carbachol-induced PH stimulation. SB-334867 decreased FWL compared to DMSO controls. These data are suggestive that stimulating the PH produces antinociception in a neuropathic pain model and that the antinociceptive effect is mediated in part by orexin-1 receptors in the spinal cord dorsal horn.
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The different alleles of the apolipoprotein E gene (APOE-gene, ApoE-protein) have been reported to influence recovery after traumatic brain injury (TBI) in both human patients and animal models, with the e4 allele typically conferring poorer prognosis for recovery. How the E4 allele, and consequently the ApoE4 isoform, affects recovery is unknown, but proposed mechanisms include neurogenesis, inflammatory response and amyloid processing or metabolism. Using the controlled cortical impact (CCI) model of brain injury and microarray technology we have characterized the genomic response to injury in the brains of APOE2, APOE3 and APOE4 transgenic mice and identified quantitatively and qualitatively significantly different profiles of gene expression in both the hippocampus and the cortex of the APOE3 mice compared to APOE4. The observed gene regulation predicts functional consequences including effects on inflammatory processes, cell growth and proliferation, and cellular signaling, and may suggest that the poor recovery post-TBI in APOE4 animals and human patients is less likely to result from a specific activation of neurodegenerative mechanisms than a loss of reparative capability.