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Propagation of neuronal micronuclei regulates microglial characteristics.
Nat Neurosci
January 2025
School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period.
View Article and Find Full Text PDFActivation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure.
Sci Adv
January 2025
Department of Neuroscience, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC).
View Article and Find Full Text PDFNeuron-derived extracellular vesicles as a liquid biopsy for brain insulin dysregulation in Alzheimer's disease and related disorders.
Alzheimers Dement
January 2025
Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Extracellular vesicles (EVs) have emerged as novel blood-based biomarkers for various pathologies. The development of methods to enrich cell-specific EVs from biofluids has enabled us to monitor difficult-to-access organs, such as the brain, in real time without disrupting their function, thus serving as liquid biopsy. Burgeoning evidence indicates that the contents of neuron-derived EVs (NDEs) in blood reveal dynamic alterations that occur during neurodegenerative pathogenesis, including Alzheimer's disease (AD), reflecting a disease-specific molecular signature.
View Article and Find Full Text PDFDistinct Behavioral Profiles and Neuronal Correlates of Heroin Vulnerability Versus Resiliency in a Multi-Symptomatic Model of Heroin Use Disorder in Rats.
Am J Psychiatry
January 2025
Department of Neuroscience, Medical University of South Carolina, Charleston (Kuhn, Crow, Walterhouse, Chalhoub, Dereschewitz, Roberts, Kalivas); School of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, Italy (Cannella, Lunerti, Ciccocioppo); Interdisciplinary Ph.D. Program in Biostatistics (Gupta) and Department of Biomedical Informatics (Gupta, Allen, Chung), and Pelotonia Institute for Immuno-Oncology, James Comprehensive Cancer Center, Ohio State University, Columbus (Gupta, Allen, Chung); Department of Internal Medicine, Wake Forest University, Winston-Salem, NC (Cockerham, Beeson, Solberg Woods); Department of Psychology, Jacksonville State University, Jacksonville, AL (Nall); Institute for Genomic Medicine, University of California San Diego, La Jolla (Palmer); School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland (Hardiman).
Objective: The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting the translational relevance of the mechanistic research that is conducted in experimental animals. The authors hypothesized that a nonlinear clustering of OUD-like behavioral traits would capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles.
Methods: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors.
Anything but small: Microarousals stand at the crossroad between noradrenaline signaling and key sleep functions.
Neuron
January 2025
Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA. Electronic address:
Continuous sleep restores the brain and body, whereas fragmented sleep harms cognition and health. Microarousals (MAs), brief (3- to 15-s-long) wake intrusions into sleep, are clinical markers for various sleep disorders. Recent rodent studies show that MAs during healthy non-rapid eye movement (NREM) sleep are driven by infraslow fluctuations of noradrenaline (NA) in coordination with electrophysiological rhythms, vasomotor activity, cerebral blood volume, and glymphatic flow.
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