Immunity, Год журнала: 2023, Номер 56(9), С. 1983 - 1985
Опубликована: Сен. 1, 2023
Язык: Английский
Molecular Psychiatry, Год журнала: 2024, Номер 29(9), С. 2821 - 2833
Опубликована: Март 29, 2024
In the brain, astrocytes regulate shape and functions of synaptic vascular compartments through a variety released factors membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to onset severe pathologies. Clinical pre-clinical studies show alterations in cell number, morphology, molecular makeup astrocyte-dependent processes different affected regions neurodevelopmental (ND) neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate mature during critical period early postnatal time window elevated glia-dependent regulation proper balance between synapse formation/elimination, which is pivotal refining connectivity. Therefore, any intrinsic and/or extrinsic altering these may result an aberrant remodeling mental The peculiar bridging position further allows them "compute" state consequently secrete bloodstream, serve as diagnostic biomarkers distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis astrocyte-mediated neuronal network periods focusing elimination. We then propose alternative hypotheses for involvement aberrancies ND NP light well-known differential prevalence certain disorders males females, also discuss putative sex-dependent influences events. From translational perspective, understanding age- astrocyte-specific functional changes help identify cellular (dys)functions health disease, favouring development tools selection tailored treatment options male/female patients.
Язык: Английский
Процитировано
26
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Дек. 1, 2023
Pooled optical screens have enabled the study of cellular interactions, morphology, or dynamics at massive scale, but not yet leveraged power highly-plexed single-cell resolved transcriptomic readouts to inform molecular pathways. Here, we present Perturb-FISH, which bridges these approaches by combining imaging spatial transcriptomics with parallel detection in situ amplified guide RNAs. We show that Perturb-FISH recovers intracellular effects are consistent Perturb-seq results a screen lipopolysaccharide response cultured monocytes, and uncover new intercellular density-dependent regulation innate immune response. further pair functional readout autism spectrum disorder risk genes, showing common calcium activity phenotypes induced pluripotent stem cell derived astrocytes their associated genetic interactions dysregulated is thus generally applicable method for studying associations biology resolution.
Язык: Английский
Процитировано
17
Cell, Год журнала: 2024, Номер unknown
Опубликована: Сен. 1, 2024
Язык: Английский
Процитировано
7
Cell & Bioscience, Год журнала: 2024, Номер 14(1)
Опубликована: Апрель 1, 2024
Abstract Background Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed assess the role of microglia and complement C1q sevoflurane-induced neurotoxicity explore underlying mechanisms. Methods Neonatal mice were treated with on postnatal days 6, 8, 10, Morris water maze was performed cognitive functions. For mechanistic explorations, minocycline, C1q-antibody ANX005, sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction engulfment analysis, immunofluorescence, microglial morphology analysis performed. In vitro experiments conducted cell line BV2 cells. Results resulted deficiencies learning cognition mice, accompanied by activation synapse loss. Sevoflurane enhanced microglia-mediated elimination through binding synapses. Inhibition phagocytosis minocycline significantly reduced loss further revealed involvement neuronal sialic acids this process. The activity sialidase acids, which facilitated ANX005 or inhibition NADNA rescued improved function. cells, reversed ANX005. Conclusions Our findings demonstrated that C1q-mediated synaptic enhancing desialylation contributed developmental neurotoxicity. may be a potential therapeutic strategy for
Язык: Английский
Процитировано
6
Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 63 - 79
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Cell Reports, Год журнала: 2025, Номер 44(1), С. 115126 - 115126
Опубликована: Янв. 1, 2025
Highlights•MBP exposure promotes NSC differentiation into astrocytes and astrocyte reactivity•MBP impairs cognitive function by increasing astrocyte-induced synapse phagocytosis•MBP affects reactivity through IRE1α/XBP1s pathwaySummaryHumans are widely exposed to phthalates, a common chemical plasticizer. Previous cohort studies have revealed that maternal monobutyl phthalate (MBP), key metabolite of is associated with neurodevelopmental defects. However, the molecular mechanism remains unclear. Here, we demonstrate MBP enhances neural stem cell (NSC) highly expressed C3 LCN2 in mouse offspring, resulting increased phagocytosis dysfunction. Mechanistically, find activates (spliced XBP1) stress response pathway, which regulates genes involved (SOX9 ATF3) (C3 LCN2). Conditional knockout or pharmacological inhibition IRE1α markedly inhibits reactivity, attenuates phagocytosis, improves function. This phenotype further recapitulated human brain organoid model. Together, these findings unveil underlying deficits caused widespread environmental pollutant.Graphical abstract
Язык: Английский
Процитировано
0
Progress in brain research, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Neuroscience, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Neuron, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Revista Brasileira de Enfermagem, Год журнала: 2025, Номер 78(suppl 2)
Опубликована: Янв. 1, 2025
ABSTRACT Objectives: to identify the occurrence of adverse childhood experiences (ACEs) among children classified as high-risk at birth. Methods: this quantitative, cross-sectional, and descriptive study was conducted within an Intermunicipal Health Consortium in Paraná from September 2022 February 2023, involving 45 caregivers children. Data collection took place participants’ homes using three questionnaires. The results were analyzed descriptively, based on theory events tree. Results: prevalence 18.6%. Regarding types events, 64.3% reported violence; 28% parental divorce; 22.2% substance abuse by caregivers; 73.3% experienced difficulty acquiring basic necessities; 62.2% unemployed and/or had low income; 55.6% lived conflict-prone areas; 44.4% lacked access sewage systems. Conclusions: are multifactorial cross-sectoral, posing significant threats child development. 2030 Agenda proposes dimensions for addressing issue investing childhood.
Язык: Английский
Процитировано
0