Neuroscience
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Uremic pruritus (UP) significantly compromises the quality of life in patients with end-stage renal disease undergoing peritoneal dialysis. Although the precise pathophysiological mechanisms of UP remain elusive, the thalamus, which is integral to processing sensory information, is potentially implicated in its development. This study aimed to investigate alterations in the structure and resting-state functional connectivity (rsFC) of thalamic subregions in patients with UP. ⋯ The decreased volume of thalamic subregions and rsFC were closely associated with UP severity. It was found that the volume of R_Stha directly influences the severity of pruritus in UP patients, but this effect does not manifest through rsFC between R_Stha and left supplementary motor area or left paracentral lobule. Patients with UP exhibited changes in structural and functional connectivity within specific thalamic subregions, providing neuroimaging insights into the neural mechanisms of UP.
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Peripuberty is a significant period of neurodevelopment with long-lasting effects on the brain and behavior. Blocking type 1 corticotropin-releasing factor receptors (CRFR1) in neonatal and peripubertal rats attenuates detrimental effects of early-life stress on neural plasticity, behavior, and stress hormone action, long after exposure to the drug has ended. CRFR1 antagonism can also impact neural and behavioral development in the absence of stressful stimuli, suggesting sustained alterations under baseline conditions. ⋯ In the adult amygdala, peripubertal CRFR1a induced alterations in pathways related to neural plasticity and stress in males. In females, pathways related to central nervous system myelination, cell junction organization, and glutamatergic regulation of synaptic transmission were affected. Understanding how acute exposure to neuropharmacological agents can have sustained impacts on brain and behavior, in the absence of further exposures, has important clinical implications for developing adolescents.
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Corticosteroid signaling plays a critical role in modulating the neural systems underlying reward and addiction, but the specific contributions of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the medial prefrontal cortex (mPFC) to opioid reward and dopaminergic plasticity remain unclear. Here, we investigated the effects of intra-mPFC injection of corticosteroid receptor ligand (corticosterone; CORT), glucocorticoid receptor antagonist (RU38486; RU), and mineralocorticoid receptor antagonist (spironolactone; SP) on morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) expression in the mPFC. Adult male Wistar rats received intra-mPFC injections of CORT, RU, SP, or their respective vehicles prior to morphine CPP conditioning. ⋯ These findings demonstrate that corticosteroid receptor signaling within the mPFC modulates the rewarding properties of morphine and morphine-induced dopaminergic plasticity. This preclinical study suggests that targeting GRs and MRs in the mPFC could be a possible therapeutic approach for treating opioid addiction. By targeting these receptors, it may be possible to reduce opioid reward and counteract the neuroadaptations in dopamine systems associated with addiction.
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Acute peripheral vestibular dysfunction is associated with a variety of postural and balance disturbances. Vestibular rehabilitation training (VRT) is widely acknowledged as an effective intervention for promoting vestibular compensation. Nevertheless, the broader implementation of early VRT is hindered by an incomplete understanding of its neurobiological mechanisms. ⋯ Our findings suggest that VRT facilitates the recovery of postural motor deficits during vestibular compensation, likely mediated by cell proliferation and glial responses, particularly the proliferation of microglia, in the MVN. Furthermore, we demonstrate that ultra-early rehabilitation training yields greater benefits for the long-term recovery of dynamic deficits following UVN. These results carry significant implications for the clinical implementation of early VRT in patients experiencing acute peripheral vestibular dysfunction.