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Neuroinflammation and microglia significantly contribute to Alzheimer’s disease pathology, depending on their activation state. We found that TREM2-expressing microglia are a heterogenous population spanning activated to senescent cells.
The study of the female brain during pregnancy and motherhood is gaining traction, and holds the potential to address the unmet needs of millions of women worldwide. Here we highlight the most pressing gaps in this field. Filling these knowledge gaps will require two paths forward: focused longitudinal studies that deeply characterize individuals, and collaborative initiatives that build large-scale international databases.
Using human iPSC-derived and mouse neurons, this study demonstrates that mRNA transport on lysosome-related vesicles is critical for the maintenance of axonal homeostasis and that its failure causes axonal degeneration.
In the first comprehensive mRNA isoform atlas of the developing and adult mouse brain, we discover that region and age influence the isoform repertoire of cell subtypes. We link peak cell type regulation to the critical development period and report attenuated levels in adulthood.
RNA alternative splicing is involved in determining cell identity, but a comprehensive molecular map is missing. Here, the authors provide a human and mouse brain atlas of transcript isoforms linking them to cellular identity, brain regions and development stages.
Precise profiling of dendritic RNA regulation reveals how neuronal depolarization leads to ribosome switching onto short upstream open reading frames and new coding sequences to acutely modulate local protein synthesis.
How astrocytes can integrate information is incompletely understood. Here the authors show that locus coeruleus-controlled calcium signals in hippocampal astrocytes propagating from their processes to their soma are involved in the information integration upon salient events.
Silva et al. definitively establish climbing fiber-driven complex spike events as essential instructive signals for associative cerebellar learning while also revealing unexpected features of optogenetic manipulation.
Human microglia transplanted in the mouse brain mount a multipronged response to amyloid-β pathology, displaying unique transcriptional states. Alzheimer’s disease risk genes are differentially regulated across cell states and profoundly alter microglial function.
The role of TREM1 in neurodegenerative diseases is unclear. Here the authors show that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology in a mouse model of Alzheimer disease.
Brain region-specific oligodendrocyte population dynamics are unclear. Here the authors implement long-term in vivo three-photon imaging to determine those dynamics in the cortical and subcortical areas in the living intact and demyelinated adult mouse brain.
The Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas is a resource of personalized brain network topographies (n = 9,900). It also provides a probabilistic atlas and integration zones across diverse magnetic resonance imaging (MRI) datasets and ages. The atlas increases the reliability of brain-wide association studies (BWAS) and improves targeting for neuromodulation.
Oligodendrocytes are vulnerable to chemical toxicity during development. However, few environmental chemicals have been identified as potential hazards. Here, the authors discover chemicals in common household products as harmful to oligodendrocyte development.
The authors find that Piezo1 stimulation enhances meningeal lymphatics and boosts CSF drainage to treat hydrocephalus and ventriculomegaly, showing promise in Down syndrome and hydrocephalus models.