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Neuroactive steroids (NASs) have potent anxiolytic, anticonvulsant, sedative, and hypnotic actions, that reflect in part their efficacy as GABA A R positive allosteric modulators (PAM). In addition to this, NAS exert metabotropic effects on GABAergic inhibition via the activation of membrane progesterone receptors (mPRs), which are G-protein coupled receptors. mPR activation enhances the phosphorylation of residues serine 408 and 409 (S408/9) in the β3 subunit of GABA A Rs, increasing their accumulation in the plasma membrane leading to a sustained increase in tonic inhibition. To explore the significance of NAS-induced phosphorylation of GABA A Rs, we used mice in which S408/9 in the β3 subunit have been mutated to alanines, mutations that prevent the metabotropic actions of NASs on GABA A R function while preserving NAS allosteric potentiation of GABAergic current. While the sedative actions of NAS were comparable to WT, their anxiolytic actions were reduced in S408/9A mice. Although the induction of hypnosis by NAS were maintained in the mutant mice the duration of the loss of righting reflex was significantly shortened. Finally, ability of NAS to terminate diazepam pharmacoresistant seizures was abolished in S408/9A mice. In conclusion, our results suggest that S408/9 in the GABA A R β3 subunit contribute to the anxiolytic and anticonvulsant efficacy of NAS, in addition to their ability to regulate the loss of righting reflex.Nexmif is mainly expressed in the central nervous system (CNS) and plays important roles in cell migration, cell to cell and cell-matrix adhesion, and maintains normal synaptic formation and function. Nevertheless, it is unclear how nexmif is linked to motor neuron morphogenesis. Here, we provided in situ hybridization evidence that nexmifa (zebrafish paralog) was localized to the brain and spinal cord and acted as a vital regulator of motor neuron morphogenesis. Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. Importantly, RNA-sequencing showed that nexmifa-depleted zebrafish embryos caused considerable CNS related gene expression alterations. Differentially expressed genes (DEGs) were mainly involved in axon guidance and several synaptic pathways, including glutamatergic, GABAergic, dopaminergic, cholinergic, and serotonergic synapse pathways, according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. In particular, when compared with other pathways, DEGs were highest (84) in the axon guidance pathway, according to Organismal Systems. Efna5b, bmpr2b, and sema6ba were decreased markedly in nexmifa-depleted zebrafish embryos. Moreover, both overexpression of efna5b mRNA and sema6ba mRNA could partially rescued motor neurons morphogenesis. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.Methamphetamine (METH), a psychostimulant, has the potential to cause neurodegeneration by targeting the cerebrum and cerebellum. It has been suggested that the NLRP3 inflammasome may be responsible for the neurotoxicity caused by METH. However, the role of NLRP3 in METH-induced cerebellar Purkinje cell (PC) degeneration and the underlying mechanism remain elusive. This study aims to determine the consequences of NLRP3 modulation and the underlying mechanism of chronic METH-induced cerebellar PC degeneration. In METH mice models, increased NLRP3 expression, PC degeneration, myelin sheath destruction, axon degeneration, glial cell activation, and motor coordination impairment were observed. Using the NLRP3 inhibitor MCC950, we found that inhibiting NLRP3 alleviated the above-mentioned motor deficits and cerebellar pathologies. Furthermore, decreased mature IL-1β expression mediated by Caspase 1 in the cerebellum may be associated with the neuroprotective effects of NLRP3 inflammasome inhibition. Collectively, these findings suggest that mature IL-1β secretion mediated by NLRP3-ASC-Caspase 1 may be a critical step in METH-induced cerebellar degeneration and highlight the neuroprotective properties of inflammasome inhibition in cerebellar degeneration.Exercise can help inhibition of neuropathic pain (NP), but the related mechanism remains being explored. In this research, we performed the effect of swimming exercise on the chronic constriction injury (CCI) rats. Compared with CCI group, the mechanical withdrawal threshold of rats in the CCI-Swim group significantly increased on the 21st and 28th day after CCI surgery. Second-generation RNA-sequencing technology was employed to investigate the transcriptomes of spinal dorsal horns in the Sham, CCI, and CCI-Swim groups. On the 28th day post-operation, 306 intersecting long non-coding RNAs (lncRNAs) and 173 intersecting mRNAs were observed between the CCI vs Sham group and CCI-Swim vs CCI groups. Then, the biological functions of lncRNAs and mRNAs in the spinal dorsal horn of CCI rats were then analyzed. Taking the results together, this study could provide a novel perspective for the treatment for NP.

Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy.

We aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies.

We prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage atent is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.

The motor imagery brain computer interface (MI-BCI) is now available in a commercial product for clinical rehabilitation. However, MI-BCI is still a relatively new technology for commercial rehabilitation application and there is limited prior work on the frequency effect. The MI-BCI has become a commercial product for clinical neurological rehabilitation, such as rehabilitation for upper limb motor dysfunction after stroke. However, the formulation of clinical rehabilitation programs for MI-BCI is lack of scientific and standardized guidance, especially limited prior work on the frequency effect. Therefore, this study aims at clarifying how frequency effects on MI-BCI training for the plasticity of the central nervous system.

Sixteen young healthy subjects (aged 22.94 ± 3.86 years) were enrolled in this randomized clinical trial study. Subjects were randomly assigned to a high frequency group (HF group) and low frequency group (LF group). The HF group performed MI-BCI training once per day while the LF gmilar effects were found in the LF group. This pilot study provided an essential reference for the formulation of clinical programs for MI-BCI training in improvement for upper limb dysfunction.Some important clinical characteristics of major depressive disorder (MDD) differ between sexes. We explored abnormal spontaneous neuronal activity in MDD patients using the amplitude of low-frequency fluctuation (ALFF) and its relationship to clinical manifestations in male and female patients, to seek the neural mechanisms underlying sex-related differences in depression. Twenty-five male MDD patients, 36 female MDD patients, and 25 male and 36 female matched healthy controls (HC) were included. The ALFF difference was investigated among four groups, and partial correlation analysis was used to explore a possible clinical relevance. The main effect results of sex difference were located in the bilateral caudate nucleus and posterior cingulate gyrus. Post hoc comparisons found that the male MDD patients showed decreased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus when compared with female MDD patients/female HCs, and female MDD patients showed increased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus when compared with male HCs. The average ALFF of the right caudate nucleus was positively correlated with illness duration in female MDD patients. Our results suggest that the sex-specific abnormal brain activity might be a potential pathomechanism of different symptoms in male and female MDD patients.Mild-to-moderate depression (MMD) is frequently encountered in clinical practice. Investigating the brain mechanism and its relationship with symptoms in patients with MMD can help us understand the occurrence and development of depression, thus optimizing the prevention and treatment of depression. Shugan Jieyu capsule (SG), a traditional Chinese medicine, is commonly used to ameliorate emotional and cognitive symptoms induced by patients with MMD. Plinabulin VDA chemical Combining clinical assessments and magnetic resonance imaging (MRI), we obtained the emotional and cognitive status of MMD patients and also explored the structural and functional alterations in MMD patients after SG treatments. Structural MRI demonstrated that the gray matter volumes of the left thalamus, right thalamus, and right amygdala in MMD patients were significantly smaller than in healthy controls, and the right amygdala volume was negatively related to depression symptoms in MMD patients. Resting-state functional MRI data demonstrated that MMD patients exhibited decreased temporal coupling between the right amygdala and nucleus accumbens, which was further associated with the severity of depression. Furthermore, right amygdala volume at baseline served as a significant predictor to identify the treatment outcome after 8 weeks of SG treatment in the patients' group, and importantly, the memory ability mediated the relationship from right amygdala volume to the treatment outcome. These data revealed the structural and functional deficits in the right amygdala, which were highly correlated with the symptoms of depression and its cognitive ability, likely predicting treatment outcome. Therefore, this study strengthened our understanding of the pathogenesis of MMD, which is hoped that it will contribute to tailoring a personalized method for treating the patients.Recently, we proposed a model of tinnitus development based on a physiological mechanism of permanent optimization of information transfer from the auditory periphery to the central nervous system by means of neuronal stochastic resonance utilizing neuronal noise to be added to the cochlear input, thereby improving hearing thresholds. In this view, tinnitus is a byproduct of this added neuronal activity. Interestingly, in healthy subjects auditory thresholds can also be improved by adding external, near-threshold acoustic noise. Based on these two findings and a pilot study we hypostatized that tinnitus loudness (TL) might be reduced, if the internally generated neuronal noise is substituted by externally provided individually adapted acoustic noise. In the present study, we extended the data base of the first pilot and further optimized our approach using a more fine-grained adaptation of the presented noise to the patients' audiometric data. We presented different spectrally filtered near-threshold noises (-2 dB to +6 dB HL, 2 dB steps) for 40 s each to 24 patients with tonal tinnitus and a hearing deficit not exceeding 40 dB.