Neuroscience
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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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Reconsolidation results in the restabilisation, and thus persistence, of a memory made labile by retrieval, and interfering with this process is thought to enable modification or weakening of the original trace. As such, reconsolidation-blockade has been a focus of research aiming to target the maladaptive memories underlying mental health disorders, including post-traumatic stress disorder and drug addiction. Current first-line therapies are not effective for all patients, and a substantial proportion of those for whom therapies are effective later relapse. ⋯ These include factors such as the age and strength of memory, and can broadly be divided into two categories: intrinsic features of the targeted memory itself, and parameters of the reactivation procedure used. With maladaptive memory characteristics inevitably varying amongst individuals, manipulation of the other limitations imposed by procedural variables have been explored to circumvent the boundary conditions on reconsolidation. Although several apparently discrepant results remain to be reconciled and these limitations yet to be truly defined, many studies have produced successful results which encouragingly demonstrate that boundary conditions may be overcome using various proposed strategies to enable translation of a reconsolidation-based intervention to clinical use.
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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.
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Time estimation is fundamental for human survival. There have been increasing studies suggesting that distributed brain regions, such as the basal ganglia, cerebellum and the parietal cortex, may contribute to a dedicated neural mechanism of time estimation. However, evidence on the specific function of the subcortical and cortical brain regions and the interplay of them is scare. ⋯ Besides, the superior temporal gyrus (STG) was found essential in the difference between time estimation in visual and auditory modality. Using psychophysiological interaction (PPI) analysis, we observed an increase in the connection between left caudate and left precuneus using the left caudate as the seed region in temporal reproduction task than control task. This suggested that the left caudate is the key region connecting and transmitting information to other brain regions in the dedicated brain network of time estimation.
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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.