Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Trends in Immunology, Journal Year: 2024, Volume and Issue: 45(5), P. 346 - 357
Published: April 16, 2024
Language: Английский
Citations
13
Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115176 - 115176
Published: Jan. 1, 2025
Microglia, the resident macrophages of brain, are derived from yolk sac and colonize brain before blood-brain barrier forms. Once established, they expand locally require Colony-stimulating-factor-1 receptor (CSF1R) signaling for their development maintenance. CSF1R inhibitors have been used extensively to deplete microglia in healthy diseased brain. In this study, we demonstrated sex-dependent differences microglial response inhibitor PLX3397. Male mice exhibited greater depletion compared females. Transcriptomic flow cytometry analysis revealed sex-specific remaining population, with female upregulating autophagy proteostasis pathways while male increased mitobiogenesis. Furthermore, manipulating key receptors by using different transgenic mouse lines resulted changes efficacies that were also sex dependent. These findings suggest survival mechanisms, which might contribute well-documented various neurological disorders.
Language: Английский
Citations
0
Neurobiology of Stress, Journal Year: 2025, Volume and Issue: unknown, P. 100714 - 100714
Published: Feb. 1, 2025
Language: Английский
Citations
0
Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(3)
Published: March 1, 2025
Despite extensive, cross-disciplinary research revealing a relationship between early life stress (ELS) and an increased risk for neuropsychiatric disorders, the underlying processes mediating this are not fully understood. Further, majority of preclinical studies investigating have taken sex differences into consideration. A growing body work suggests that microglia, resident immune cells brain, impacted by ELS contribute to some maladaptive behavioral phenotypes in adulthood. Here, we utilized adolescent social isolation (aSI) model female rats test role microglia effects on anxiety-related behaviors. The present study sought determine whether ablation during aSI could prevent anxiety-like behaviors Long Evans rats. colony-stimulating factor 1 receptor (CSF1-r) inhibitor, PLX3397, was provided chow ablate at start period (postnatal day (P) 21-42). During period, animals performed battery assays including open field test, elevated plus maze, successive alleys test. Following completion assays, brain tissue collected confirm efficacy PLX3397 identify changes population density. Relative group-housed (GH) controls, showed locomotor activity higher closed-arm entries maze. Although effectively ablated across all animals, treatment had minimal observed aSI-associated phenotypes. Together, these data suggest required adaptations promoted aSI. Future will be needed assess
Language: Английский
Citations
0
Cell stem cell, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Widespread delivery of therapeutic proteins to the brain remains challenging. To determine whether human induced pluripotent stem cell (iPSC)-microglia (iMG) could enable brain-wide and pathology-responsive cargo, we utilized CRISPR gene editing engineer iMG express Aβ-degrading enzyme neprilysin under control plaque-responsive promoter, CD9. further increased engraftment enhances efficacy, a CSF1R-inhibitor resistance approach. Interestingly, both localized in Alzheimer's disease (AD) mice reduced multiple biochemical measures pathology. However, within plaque-dense subiculum, reductions plaque load, dystrophic neurites, astrogliosis preservation neuronal density were only achieved following widespread microglial engraftment. Lastly, examined chimeric models breast cancer metastases demyelination, demonstrating that adopt diverse transcriptional responses differing neuropathologies, which be harnessed therapeutics CNS.
Language: Английский
Citations
0
Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(4), P. 45 - 45
Published: April 17, 2025
To investigate the role of microglial subtypes in mouse visual cortex development, focusing on ocular dominance plasticity and interactions with GABAergic neurons extracellular matrix. Immunofluorescence single-nucleus RNA-sequencing (snRNA-seq) were used to study microglia binocular primary (V1) from postnatal day (P) 11 P42. Gene ontology (GO) analysis assessed synapse organization, impact disruption was examined. Visual evoked potentials miniature postsynaptic current recordings are monitor functional changes V1. Microglia underwent a marked expansion between P11 P21 stabilized after P35, coinciding notable gene expression that aligned synaptic remodeling. GO at P14 P28 revealed significant enrichment organization linked microglia. Single-nucleus RNA sequencing identified six distinct clusters, among which two functionally relevant subpopulations closely cortical plasticity. One cluster, enriched inflammatory responses endocytosis, peaked P21, whereas another associated signaling, exhibited dynamic eye opening during critical period, significantly influencing In parallel, perineuronal nets (PNNs) PV(+) interneuron populations increased reached steady levels by P42, suggesting help coordinate timing inhibitory circuit maturation. Disrupting function period impaired plasticity, but this effect reversed treatment cessation. Mechanistically, depletion enhanced numbers, elevated PNN expression, altered development. Our findings highlight specific as key regulators development through their interneurons PNNs. These insights advance our understanding contributions provide potential avenues for targeting modulate
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: April 14, 2024
Abstract The blood-brain barrier (BBB) is critical for maintaining brain homeostasis but susceptible to inflammatory dysfunction. Permeability of the BBB lipophilic molecules shows circadian variation due rhythmic transporter expression, while basal permeability polar non-rhythmic. Whether daily timing influences in response inflammation unknown. Here, we induced systemic through repeated lipopolysaccharide (LPS) injections either morning (ZT1) or evening (ZT13) under standard lighting conditions, then examined a molecule, sodium fluorescein. We observed clear diurnal permeability, with striking increase paracellular leak across specifically following LPS injection. Evening led persisting glia activation and that was not periphery. exaggerated neuroinflammation disruption were suppressed by microglial depletion keeping mice constant darkness. Our data show rhythms responses drive variability breakdown reveals time-of-day as key regulator disruption.
Language: Английский
Citations
3
Published: May 10, 2024
Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk Terman postulated lipofuscin accumulation main or at least a major driving factor aging. They even posited evolution memory reason why we get all, as stable synaptic connections must be maintained over time, meaning somas neurons also remain same locale. In other words, they cannot dilute out their time through cell division. Mechanistically, position certainly makes sense given rendering large percentage cell’s lysosomes useless almost negatively affect surrounding microenvironment. It may case issue regard to current age-related disease. Degradation situ an insurmountable task currently. However, method systemic removal discussed herein.
Language: Английский
Citations
1
Published: May 13, 2024
Organ shortage is one of the most pressing issues with regard to human mortality. This issue further complicated by fact that HLA matching required for patients, leading restricted choices transplant. If organs or tissues from non- partially-HLA–matched donors could be edited such they evade cytotoxic T cells as well natural killer cells, it would ameliorate organ problem.
Language: Английский
Citations
1
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Aug. 30, 2024
Microglia are resident immune cells in the central nervous system, including retina that surveil environment for damage and infection. Following retinal damage, microglia undergo morphological changes, migrate to site of express secrete pro-inflammatory signals. In zebrafish retina, inflammation induces reprogramming proliferation Müller glia regeneration neurons following or injury. Immunosuppression pharmacological ablation reduce abolish proliferation. We evaluated architecture adult irf8 mutants, which have significantly depleted numbers microglia. show mutants normal structure at 3 months post fertilization (mpf) 6 mpf but fewer cone photoreceptors by 10 mpf. Surprisingly, light-induced photoreceptor induced rod regeneration. Light-damaged retinas from both wild-type upregulated expression mmp-9, il8, tnfβ cytokines. Our data demonstrate can regenerate normally acute These findings suggest may not be essential other mechanisms compensate reduction numbers.
Language: Английский
Citations
1