Neuroscience
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Cysteine protease Cathepsin S (CatS) expressed by spinal microglia has been shown to play a critical role in nerve injury and inflammation-induced chronic pain. However, whether microglial CatS contributes to remifentanil-induced acute hyperalgesia remains unstudied. In the present study, intravenous remifentanil infusion induced a significant increase in the expression of premature and mature form of CatS in the activated microglia in the spinal cord. ⋯ However, increased protein level of premature form of CatS was not affected by PBN. Altogether, our findings demonstrate that neuronal ROS promote maturation of microglial CatS which facilitates activation of NMDA in the spinal dorsal horn. Therefore, such mechanism is involved in neuron-microglia positive feedback and contributes to remifentanil-induced hyperalgesia.
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Mutations in the Pejvakin (Pjvk) gene cause autosomal recessive hearing loss DFNB59 with audiological features of auditory neuropathy spectrum disorder (ANSD) or cochlear dysfunction. The precise mechanisms underlying the variable clinical phenotypes of DFNB59 remain unclear. Here, we demonstrate that mice with conditional ablation of the Pjvk gene in all sensory hair cells or only in outer hair cells (OHCs) show similar auditory phenotypes with early-onset profound hearing loss. ⋯ Using the C-terminal domain of pejvakin as bait, we identified in a cochlear cDNA library ROCK2, an effector for the small GTPase Rho, and the scaffold protein IQGAP1, involved in modulating actin dynamics. Both ROCK2 and IQGAP1 associate via their coiled-coil domains with pejvakin. We conclude that pejvakin is required to sustain OHC activity and survival in a cell-autonomous manner likely involving regulation of Rho signaling.
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Patients with dysphagia can have higher risks of aspiration after repetitive swallowing activity due to the "fatigue effect". However, it is still unknown how consecutive swallows affect brain activity. Therefore, we sought to investigate differences in swallowing brain networks formed during consecutive swallows using a signal processing on graph approach. ⋯ The proposed algorithms were tested using synthetic signals and showed improved energy concentration in comparison to the original algorithm. When applied to EEG swallowing data, the optimized windowed graph Fourier transform and the optimized graph S-transform showed that differences exist in brain activity between consecutive swallows. In addition, the results showed higher differences between consecutive swallows for thicker liquids.
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Exposure to stress early in life may negatively impact nervous system functioning, including increasing the proneness to learning and memory impairments later in life. Maternal deprivation, a model of early-life stress, hinders memory in adult rats and lessens brain-derived neurotrophic factor (BDNF) levels in the hippocampus in a very heterogeneous way among individuals. The main goal of the present study was to investigate the possible epigenetic modulation underlying recognition memory impairment and reduced BDNF levels in the hippocampus of adult maternally deprived rats. ⋯ Moreover, we also showed that there is a positive correlation between BDNF levels and memory performance. Taken together, the results indicated that HDAC inhibitors could be considered as a possible therapeutic agent to improve cognitive performance in inferior learners. Further studies need to be conducted for a better comprehension of the mechanisms related to persistent alterations observed in adult life induced by early stressful circumstances and those leading to resilience.
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Chronic cerebral hypoperfusion (CCH) is associated with various ischemic cerebrovascular diseases that are characterized by cognitive impairment. The role of autophagy in cognitive dysfunction under conditions of CCH is poorly understood. To address this issue, the present study investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on autophagy and cognition in a CCH model as well as the underlying mechanisms. ⋯ URB597 improved cognitive impairment by inhibiting CCH-induced autophagy, which was associated with mTOR signaling. Moreover, the ultrastructural deterioration resulting from CCH was improved by chronic treatment with URB597. These findings indicate that URB597 modulates autophagy in an mTOR-dependent manner, and mitigates neuronal damage and cognitive deterioration caused by CCH.