Neuroscience
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Neonatal pain experiences including traumatic injury influence negatively on development of nociceptive circuits, resulting in persistent pain hypersensitivity in adults. However, the detailed mechanism is not yet well understood. In the present study, to clarify the pathogenesis of orofacial pain hypersensitivity associated with neonatal injury, the involvement of the voltage-gated sodium channel (Nav) 1.8 and the C-C chemokine ligand 2 (CCL2)/C-C chemokine receptor 2 (CCR2) signaling in the trigeminal ganglion (TG) in facial skin incisional pain hypersensitivity was examined in 190 neonatal facial-injured and sham male rats. ⋯ Blockages of Nav1.8 in the incised region and CCR2 in the TG suppressed the enhancement of mechanical hypersensitivity in the Incision-Incision group. Administration of CCL2 into the TG enhanced mechanical hypersensitivity in the Sham-Sham, Incision-Sham and Sham-Incision group. Our results suggest that neonatal facial injury accelerates the TG neuronal hyperexcitability following orofacial skin injury in adult in association with Nav1.8 overexpression via CCL2 signaling, resulting in the enhancement of orofacial incisional pain hypersensitivity in the adulthood.
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Neonatal seizures commonly caused by hypoxia can lead to long-term neurological outcomes. Early inflammation plays an important role in the pathology of these outcomes. Therefore, in the current study, we explored the long-term effects of Fingolimod (FTY720), an analog of sphingosine and potent sphingosine 1-phosphate (S1P) receptors modulator, as an anti-inflammatory and neuroprotective agent in attenuating anxiety, memory impairment, and possible alterations in gene expression of hippocampal inhibitory and excitatory receptors following hypoxia-induced neonatal seizure (HINS). ⋯ These effects were associated with restoration of the hippocampal thiol content to the normal values and the regulatory role of FTY720 in the expression of hippocampal GABA and glutamate receptors subunits. In conclusion, FTY720 could restore the dysregulated gene expression of excitatory and inhibitory receptors. It also increased the reduced hippocampal thiol content, which was accompanied with attenuation of HINS-induced anxiety, reduced the impaired hippocampal related memory, and prevented hippocampal LTP deficits in later life following HINS.
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The analgesic effect of opioids decreases over time due to the development of analgesic tolerance. We have shown that inhibition of the platelet-derived growth factor beta (PDGFR-β) signaling eliminates morphine analgesic tolerance in rats. Although the PDGFR-β and its ligand, the platelet-derived growth factor type B (PDGF-B), are expressed in the substantia gelatinosa of the spinal cord (SG) and in the dorsal root ganglia (DRG), their precise distribution within different cell types of these structures is unknown. ⋯ Consistent with our previous finding that morphine caused tolerance by inducing PDGF-B release, PDGF-B was upregulated in the spinal cord. We also found that chronic morphine exposure caused a spinal proliferation of oligodendrocytes. The changes in PDGFR-β and PDGF-B expression induced by chronic morphine treatment suggest potential mechanistic substrates underlying opioid tolerance.
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Iron supplementation previously demonstrated antidepressant-like effects in post-partum rats. The present study evaluates the possible synergistic antidepressant effect of sub-therapeutic dose of iron co-administered with citalopram or imipramine in female Institute of Cancer Research mice. Depression-like symptoms were induced in the forced swim (FST), tail suspension (TST), and open space swim (OSST) tests while open field test (OFT) was used to assess locomotor activity. ⋯ Our study provides experimental evidence that iron has antidepressant-like effect and sub-therapeutic dose of iron combined with citalopram or imipramine produces more rapid antidepressant-like effect. We further show that iron alone or its combination with citalopram or imipramine attenuates the neuronal loss associated with depressive conditions, increases dendritic spines density and BDNF levels. These finding suggest iron-induced neuronal plasticity in the mice brain.
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Randomized Controlled Trial
Resting state dynamics in people with varying degrees of anxiety and mindfulness: A nonlinear and nonstationary perspective.
Anxiety and mindfulness are two inversely linked traits shown to be involved in various physiological domains. The current study used resting state electroencephalography (EEG) to explore differences between people with low mindfulness-high anxiety (LMHA) (n = 29) and high mindfulness-low anxiety (HMLA) (n = 27). The resting EEG was collected for a total of 6 min, with a randomized sequence of eyes closed and eyes opened conditions. ⋯ It led us to conclude that it might be anxiety, not mindfulness, which might have contributed to higher electrophysiological arousal. Additionally, a higher δ-β and δ-γ CFC in LMHA suggested greater local-global neural integration, consequently a greater functional association between cortex and limbic system than in the HMLA group. The present cross-sectional study may guide future longitudinal studies on anxiety aiming with interventions such as mindfulness to characterize the individuals based on their resting state physiology.