Neuroscience bulletin最新文献

Alzheimer's disease (AD) is a widespread neurodegenerative condition with cognitive and behavioral decline. Astrocytes and microglia, the primary glial cells in the central nervous system, are deeply involved in AD development. Their functional impairments, such as astrocytic shifts in phenotype, blood-brain barrier breakdown, and glymphatic failure, along with microglial "dual phagocytic dysfunction", including impaired amyloid-beta (Aβ) clearance and overactive phagocytosis of healthy synapses, imbalanced inflammation, and metabolic abnormalities, are key drivers of disease progression. Growing research indicates that physical activity, as a non-drug intervention, exerts significant regulatory effects on glial cell function. Exercise regulates the polarization of both astrocytes and microglia, enhances their phagocytic abilities, improves mitochondrial metabolism, and alleviates neuroinflammatory responses. This review outlines the normal physiological roles of astrocytes and microglia, details their pathological alterations in AD, and explores how exercise targets these glial cells to alleviate AD pathology, offering valuable perspectives for potential therapeutic approaches.

Noise-induced hearing loss is a prevalent form of sensorineural hearing impairment that negatively impacts quality of life and has no effective clinical treatments. Damage due to oxidative stress in cochlear hair cells is thought to be the typical pathological basis. Oxeiptosis is oxidative stress-induced, caspase-independent modality of cell death. In this study, we found that oxeiptosis plays an important role in noise-induced hearing loss, which has not been previously identified. Using protein quantification, protein-protein interaction studies, and immunofluorescence staining in cellular models, we elucidated the pivotal molecules of oxeiptosis. Building on the in vitro experimental data, we detected characteristic protein alterations along the oxeiptosis pathway in noise-induced hearing loss murine models. Furthermore, the pharmacological suppression effectively attenuated noise-induced oxeiptosis in cochlear hair cells and partially alleviated hair cell death. This study confirms the existence of a new cell death pathway in NIHL and provides a potential treatment alternative.

Central nervous system (CNS) injuries trigger a complex glial response, in which oligodendrocyte precursor cells (OPCs) play a far more dynamic role than previously recognized. Moving beyond their canonical function as a remyelination reservoir, reactive OPCs emerge as plastic signaling hubs whose fate and function are dictated by injury-specific cues. This review synthesizes recent evidence to propose a novel conceptual framework: the "reactive OPC state code." We argue that deciphering this code-the molecular signatures that define pro-regenerative, immunomodulatory, or maladaptive OPC states-is the key to understanding functional heterogeneity in CNS injury. We critically analyze how distinct pathological contexts (trauma, ischemia, neuroinflammation) rewrite this code, leading to diverse outcomes. Finally, we pivot from a generic discussion of OPC-directed therapies to advocate for "state-specific targeting" as the next frontier in translational medicine, offering a roadmap for developing precision interventions that steer reactive OPCs towards repair. This perspective aims to redefine OPC reactivity from a passive response to a central, druggable axis in CNS pathology and repair.

Astrocytes have long been considered passive players in brain function, yet emerging evidence suggests they actively modulate neural activity and signal transmission. This study combines chemogenetics and optogenetics approaches with functional magnetic resonance imaging (fMRI) to investigate the impact of astrocyte activation on local field potentials (LFPs) and downstream BOLD signals. Using a multimodal neuroimaging approach, we explore how astrocyte activation influences electrophysiological responses in different brain regions, particularly focusing on the prefrontal cortex (PFC) and its downstream targets. Our results reveal significant increases in LFP energy within specific frequency bands, such as Theta and Delta, in response to laser stimulation. These changes demonstrate the spatial specificity of astrocyte activity and its capacity to modulate local network dynamics. Furthermore, following chemogenetic inhibition of neuronal activity, optogenetic reactivation of astrocytes continued to evoke BOLD responses, supporting the notion that astrocytes have a pivotal role in the regulation of cerebral blood flow and metabolism. These findings challenge traditional views of BOLD signal origins and emphasize the need for a reevaluation of astrocyte involvement in neurovascular coupling. This study provides novel insights into astrocyte function, offering a new perspective on brain-wide connectivity and its implications for both normal brain function and neuropathological conditions.

Retinal organoids (ROs) are three-dimensional in vitro models that replicate the specific cellular composition and inner structure of the retina. Currently, ROs derived from human pluripotent stem cells (hPSCs) have been shown to mimic both the structure and function of the human retina. Furthermore, ROs function as a powerful model system for researchers, facilitating the investigation of the pathogenesis and treatment strategies of retinal diseases. Despite their development for over a decade, ROs remain limited in terms of complexity and clinical application. This review summarizes recent advances in the development of retinal differentiation methods and underscores their potential applications in disease modeling, gene therapy, cell transplantation, and drug screening. In addition, it proposes research directions that are geared towards advancing RO methodologies to further broaden their applications.

Autism spectrum disorder (ASD) pathophysiology often involves striatal dysfunction, yet the underlying mechanisms remain unclear. Mutations in Forkhead box G1 (FOXG1) cause FOXG1 syndrome, a condition sharing core ASD features. Here, loss of Foxg1 in the indirect pathway spiny projection neurons (iSPNs) in mice recapitulates ASD symptoms, including social, language, and fine movement deficits. Foxg1 deficiency causes dendritic simplification, spine reduction, and impairs excitatory synaptic transmission. Transcriptome reveals that FOXG1 drives gene networks to multidimensionally control synaptic functions from spine morphogenesis, synaptic maturation, ion transmembrane transport, glutamate receptor clustering, to neurotransmitter release and synaptic transmission. Importantly, FOXG1 directly activates the transcription of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, and pharmacological potentiation of AMPAR activity normalizes synaptic function and rescues behavioral deficits. Our study provides a new perspective on the relationship between FOXG1 and ASD etiology in iSPNs and suggests the potential of AMPAR activation as a therapeutic intervention for ASD and FOXG1 Syndrome.