Neural Regeneration Research最新文献

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023, of which 4 studies were performed with whole blood, 4 with blood plasma, 5 with blood serum, 1 with serum neural cell adhesion molecule L1-captured extracellular vesicles, 1 with blood cells, and 2 with peripheral blood mononuclear cells. Most of the studies involved children and the study cohorts were largely males. Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression. Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls. The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p, -197-5p, -424-5p, -664a-3p, -365a-3p, -619-5p, -664a-3p, -3135a, -328-3p, and -500a-5p in blood plasma and miR-151a-3p, -181b-5p, -320a, -328, -433, -489, -572, -663a, -101-3p, -106b-5p, -19b-3p, -195-5p, and -130a-3p in blood serum of children, and miR-15b-5p and -6126 in whole blood of adults. Several important limitations were identified in the studies reviewed, and need to be taken into account in future studies. Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

Pain is often comorbid with emotional disorders such as anxiety and depression. Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission. This review primarily aims to outline the main circuitry (including the input and output connectivity) of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons; it also describes the neurotransmitters/neuromodulators affecting these neurons, their intercommunication with other neurons, and their importance in mental comorbidities associated with chronic pain disorders. Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions. However, the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive. It is also unclear as to whether the mechanisms are presynaptic or postsynaptic. Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes, one of the most common motifs found in gene promoters and enhancers. Over the last 30 years, research has revealed that the nuclear factor Y complex controls many aspects of brain development, including differentiation, axon guidance, homeostasis, disease, and most recently regeneration. However, a complete understanding of transcriptional regulatory networks, including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive. In this review, we explore the nuclear factor Y complex's role and mode of action during brain development, as well as how genomic technologies may expand understanding of this key regulator of gene expression.

JOURNAL/nrgr/04.03/01300535-202510000-00026/figure1/v/2024-11-26T163120Z/r/image-tiff Microglia, the resident monocyte of the central nervous system, play a crucial role in the response to spinal cord injury. However, the precise mechanism remains unclear. To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury, we performed single-cell RNA sequencing dataset analysis, focusing on changes in microglial subpopulations. We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis, sphingomyelin metabolism, and neuroinflammation at high levels. Subsequently, we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury. Finally, we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells. Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis. Furthermore, ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway. Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function. Pla2g7 formed a "bridge" between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway. Collectively, these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3, thereby exerting neuroprotective effects.

JOURNAL/nrgr/04.03/01300535-202510000-00030/figure1/v/2024-11-26T163120Z/r/image-tiff Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age- and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances. Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

Regulated cell death is a form of cell death that is actively controlled by biomolecules. Several studies have shown that regulated cell death plays a key role after spinal cord injury. Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords. Autophagy, a complex form of cell death that is interconnected with various regulated cell death mechanisms, has garnered significant attention in the study of spinal cord injury. This injury triggers not only cell death but also cellular survival responses. Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis, ferroptosis, and autophagy. Therefore, this review aims to comprehensively examine the mechanisms underlying regulated cell deaths, the signaling pathways that modulate these mechanisms, and the potential therapeutic targets for spinal cord injury. Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury. Moreover, a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Alzheimer's disease is a common neurodegenerative disorder defined by decreased reasoning abilities, memory loss, and cognitive deterioration. The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer's disease. The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years. As a safe and feasible therapeutic and drug-delivery method, ultrasound has shown promise in improving cognitive deficits. This article provides a summary of the application of ultrasound technology for treating Alzheimer's disease over the past 5 years, including standalone ultrasound treatment, ultrasound combined with microbubbles or drug therapy, and magnetic resonance imaging-guided focused ultrasound therapy. Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms. We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-β plaque deposition. We believe that ultrasound is an effective therapy for Alzheimer's disease, and this review provides a theoretical basis for future ultrasound treatment methods.

JOURNAL/nrgr/04.03/01300535-202510000-00031/figure1/v/2024-11-26T163120Z/r/image-tiff Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum. However, their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target. In addition, the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure. To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides, we used a C57BL/6J mouse model treated with kanamycin. We found that the mice exhibited auditory deficits following the acute loss of outer hair cells. Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time. Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response, particularly those related to the NLRP3 inflammasome. Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed, accompanied by infiltration of macrophages and the release of proinflammatory cytokines. Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model. These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration. Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.