This year’s researchers bring expertise in computational biology, immunology, neuroscience, and cellular engineering.

This year’s researchers bring expertise in computational biology, immunology, neuroscience, and cellular engineering.

The authors identify glucose-derived conversion of citrate to acetyl-CoA upstream of histone acetylation as modulating the regional dynamics of oligodendrocyte progenitors, with extranuclear acetyl-Co...

In vivo regulation of neuronal lipid droplet formation mediates whole-body energy homeostasis in a sex-specific manner in Drosophila and mice.

Microglial dysfunction is a hallmark of Alzheimer’s disease (AD), yet the molecular mechanisms driving these impairments remain poorly defined. Genetic studies implicate several AD-associated genes in...

The complex morphologies of neurons and glia emerge through profound changes in membrane lipids and proteins during development. Lysosomes are central…

Insights into the mechanism by which phosphatidylserine functions as a non-classical inhibitory molecule during T cell exhaustion, and how phosphatidylserine-targeting antibodies enhance T cell r...

The mechanisms underlying impaired myelination during aging remain incompletely understood. Here, Gao et al. report that ACSS2-mediated acetate utilization is essential for maintaining the oligodendro...

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understa...

This Review discusses brain lipid metabolism from a cellular perspective, focusing on lipid uptake, de novo synthesis, storage, breakdown and intercellular transfer, and highlights its emerging implic...

Peripheral macrophage-like haemocytes in Drosophila promote sleep by clearing lipid buildup in the brain, helping to maintain metabolic homeostasis and brain function and fitness.

Glial cells maintain the brain’s lipid and energy balance, and their breakdown is increasingly recognized as a causal contributor to Alzheimer’s disease (AD). While this concept is established, no approach has directly shown how glial homeostatic failure manifests across brain regions and microenvironments or how it links local pathology, such as plaques, to global metabolic imbalance. To address this gap, we developed iMIST, an integrated platform that combines MALDI-based metabolite imaging, histology, and spatial transcriptomics within a single tissue section to align molecular and anatomical information. Using a mouse model of late-onset AD that recapitulates both amyloid deposition and metabolic vulnerability, iMIST revealed that glial lipid dysregulation is widespread but spatially specialized. In gray matter, plaque-associated microglia were associated with upregulated glycerophospholipid-remodeling in cortico-thalamic areas indicating metabolic stress around local pathology. In contrast, white matter tracts rich in lipid-producing oligodendrocytes show plaque-independent deficits in galactosylceramide metabolism reflecting their high myelin demand. Both processes intensify with age, transforming adaptive glial responses into persistent metabolic dysfunction. Together, these findings demonstrate the spatial interplay between global glial metabolic imbalance and local microenvironmental stressors associated with AD pathology. By integrating transcriptomic and metabolomic information in situ , iMIST provides a framework for uncovering how regional glial vulnerability shapes the pathogenesis of neurodegenerative diseases. ### Competing Interest Statement The authors have declared no competing interest. NIH, R01NS130876, R01AI178795, R01AI149699, R42GM143989, P01AG002132, R01AG082141

Oligodendrocytes form myelin sheaths around axons to enable rapid signaling within neural circuits. The generation of new oligodendrocytes through differentiation of oligodendrocyte precursor cells (O...

Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipids are often assumed …

Obesity is a worldwide health crisis, with unhealthy diet as a major contributor. Comorbid neuropsychiatric conditions such as depression and anxiety are associated with obesity. Since obesity is a pro-inflammatory state, chronic neuroinflammation may mediate obesity and neuropsychiatric comorbidity. We used RNA-seq to provide a single-cell resolution transcriptome of brain immune cells using long-term high-fat diet (HFD) to model obesity in male mice. HFD mice exhibited depression and anxiety-like behavior. We observed a shift towards increased proportions of lipid droplet-accumulating microglia (LDAM) in the long-term HFD brain. By in-depth characterization of the transcriptional signature of LDAM, we identified that ACSL1, a key regulator of lipid droplet biogenesis, was highly expressed in LDAM induced by HFD. Finally, we demonstrated that ACSL1 inhibition reduced lipid droplets deposition in microglia exposed to free fatty acids (FFA). Our findings provide a comprehensive view of the molecular changes in brain immune cells associated with HFD, suggesting a link between microglial lipid droplet accumulation and neurological comorbidities induced by obesity.

Neurons are shown to use fatty acid β-oxidation as a fuel source for memory formation upon intensive learning in Drosophila, challenging the view that neurons are unable to use fatty acids for energy ...

This postdoc uncovers how glial dysfunction drives neurodegeneration in a rare movement disorder.