Glucose-dependent spatial and temporal modulation of oligodendrocyte progenitor cell proliferation via ACLY-regulated histone acetylation - Nature Neuroscience

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...

nature.com

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis - Nature Metabolism

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

nature.com

Alzheimer’s disease risk protein SorLA regulates ER homeostasis and lipid metabolism in human microglia, with conserved effects in neurons - Acta Neuropathologica

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...

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Lysosomal salvage of neuronal lipids enables glial infiltration of synaptic regions

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

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Exposed phosphatidylserine is an inhibitory molecule in T cell exhaustion - Nature

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...

nature.com

ACSS2 maintains oligodendrocyte progenitor cell pool and is required for myelination during development and aging - Nature Aging

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...

nature.com

Intestinal macrophages modulate synucleinopathy along the gut–brain axis - Nature

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...

nature.com

Cellular mechanisms of brain lipid metabolism in health and disease - Nature Cell Biology

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...

nature.com

Sleep-dependent clearance of brain lipids by peripheral blood cells - Nature

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.

nature.com

Spatially resolved transcriptome–metabolome integration reveals region-specific glial lipid dysregulation associated with Alzheimer’s pathology

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

biorxiv.org

biorxiv.org

Myelin is repaired by constitutive differentiation of oligodendrocyte progenitors

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...

science.org

Inducible deletion of DGAT1 and 2 from microglia exacerbates neurodegeneration and endolysosomal lipid accumulation in male PS19 mice

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

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Single-cell RNA sequencing uncovers molecular features underlying microglial lipid accumulation and depression-related behaviors in high-fat diet mouse model of obesity | Neuropsychopharmacology

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.

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Neuronal fatty acid oxidation fuels memory after intensive learning in Drosophila - Nature Metabolism

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 ...

nature.com

Postdoc Portrait: Priya Prakash

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

the-scientist.com

biorxiv.org

Advances in the genetics and pathology of Lewy body dementia

Lewy body dementia is a heterogeneous disease that is underdiagnosed and poorly understood. Pathologically, Lewy body dementia is characterised by the…

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