Neuroscience最新文献

Microglial phagocytosis is essential for neurological recovery after intracerebral hemorrhage (ICH). Using single-cell RNA sequencing, we compared microglial responses in murine and human ICH and identified striking species-specific temporal patterns. Murine microglia exhibited a sustained enhancement of phagocytic activity, whereas human microglia showed only a transient increase followed by a decline and persistent inflammation. To identify genes associated with phagocytic differences, we evaluated five machine learning models and selected XGBoost as the best-performing model. This analysis identified Tlr2 in mice and CLEC7A in humans as genes associated with microglial phagocytic status. Inferred transcription factor activity analysis further revealed stronger phagocytosis- and inflammation-associated transcriptional activity in murine phagocytic microglial subclusters, whereas human microglia were predominantly characterized by inflammation-associated transcription factors. Consistent with these results, Tlr2 expression was markedly increased at day 14 in single-cell data, and immunostaining confirmed its colocalization with IBA1⁺ microglia and upregulation at days 3 and 7 after ICH. Together, our findings demonstrate that integrating single-cell RNA sequencing with machine learning facilitates the identification of phagocytosis-associated genes and reveals both conserved and divergent patterns of microglial phagocytosis, providing new insights into species-specific responses to ICH.

Recent advances in high-throughput technologies have led to an increased generation of biological data across genomics, transcriptomics, proteomics, epigenomics, and metabolomics. However, a major challenge remains: effectively integrating these multi-omics datasets to allow a more holistic understanding of the complex, interconnected mechanisms underlying human diseases. Neurodevelopmental, neurodegenerative, and psychiatric disorders are particularly multifactorial and heterogeneous, making them candidates for multi-omics approaches. In this context, this systematic review assesses the current state of multi-omics integration in neurological research. Records retrieved from five major databases were processed, and 156 studies were included for further analysis. The most frequently studied conditions were Alzheimer's Disease, Depressive Disorder and Parkinson's Disease, with epigenomics-transcriptomics and metagenomics-metabolomics emerging as the most common omics pairings. The field remains dominated by studies integrating pairs of omics layers. Only a limited number of computational tools are currently being applied to the integration of more than two omics layers, highlighting a gap in comprehensive multi-omics modeling. Despite progress, key challenges persist, including data accessibility and the need for standardized frameworks to allow cross-study comparisons. Moreover, most computational findings lack experimental validation in wet-laboratory settings. Future research should address these challenges, develop scalable algorithms for integrating multi-omics data, and leverage large, open-access datasets. Integrating computational predictions with experimental validation could help researchers prioritize high-confidence biomarkers relevant to clinical applications. Collaborative efforts among bioinformaticians, clinicians, and experimentalists will be essential to translating these advances into clinically actionable solutions.

Mitochondrial dysfunction is a critical early driver of retinal ganglion cell (RGC) loss in optic nerve injury. We evaluated whether HDAP2, a mitochondria-targeted aromatic peptide designed to support mitochondrial membrane integrity, could preserve neuronal structure after optic nerve crush (ONC) in C57BL/6 mice (both sexes, n = 31). Systemically administered HDAP2 penetrated the blood-retinal barrier and localized to RGCs and mitochondrial-rich retinal layers. Daily treatment significantly improved RGC survival compared to saline-treated ONC animals. RGC densities increased across central, midperipheral, and peripheral regions. Transmission electron microscopy revealed that HDAP2 substantially reduced mitochondrial loss within crushed optic nerve axons. Mitochondrial density in HDAP2-treated nerves approached levels observed in uninjured controls and was nearly 3-fold higher than untreated ONC nerves. Mitochondrial morphology was similar across groups, indicating that HDAP2 prevents mitochondrial loss rather than rescuing damaged organelles. HDAP2-treated nerves also exhibited a numerically higher density of structurally intact axons, consistent with reduced ultrastructural degeneration. These findings demonstrate that HDAP2 limits mitochondrial loss and attenuates neuronal degeneration after ONC. Together, the results support HDAP2 as a promising therapeutic candidate for protecting CNS projection neurons by maintaining mitochondrial stability after axonal injury.