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Neonatal microglia replacement in mice modulates seizure severity in adulthood

ABSTRACT: Neonatal microglia replacement in mice modulates seizure severity in adulthood

PROVIDER: PRJNA1308981 | ENA |

REPOSITORIES: ENA

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Neonatal microglia replacement in mice modulates seizure severity in adulthood

Project description:Microglia replacement therapy, where endogenous brain macrophages are depleted and replaced by adoptively transferred surrogates, holds promise for treating pediatric neurologic diseases, but little is known about how early life microglia replacement impacts the brain. We sought to investigate how early postnatal microglia depletion and adoptive macrophage transfer, essential components of microglia replacement, durably impact neural circuits in a mouse model. Using both pharmacologic and genetic models, postnatal microglia depletion worsened adult seizure severity, mortality and neuropathology in a chemical seizure model. Replacement of endogenous microglia by adoptive transfer of monocytes rescued this effect, while transfer of authentic microglia from a donor mouse did not, and even worsened seizure phenotypes. RNA sequencing of transplanted microglia, monocyte-derived surrogates, and endogenous microglia revealed distinct state changes across groups in response to chemically induced seizure, demonstrating that both ontogeny and adoptive transfer significantly impact resident macrophage responses to the excitotoxic brain environment. In sum, we established models for neonatal microglia depletion and replacement, then applied them to identify durable impacts of depletion and reconstitution on the brain environment. We ultimately identified differential responses of macrophages to excitotoxic challenge based on their ontogeny, underscoring focus areas for ongoing preclinical development of microglia replacement therapies.

2025-09-15 | GSE306032 | GEO

Neonatal microglia replacement in mice modulates seizure severity in adulthood.

Project description: Not available

| S-EPMC12444772 | biostudies-literature

Neonatal injury increases gut permeability by epigenetically suppressing E-cadherin in adulthood

Project description:Neonatal injury increases gut permeability by epigenetically suppressing E-cadherin in adulthood

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Phosphoproteomic analysis of neonatal regenerative myocardium revealed important roles of CHK1 via activating mTORC1/P70S6K pathway

Project description:Restoring the regenerative capacity of myocardium, which presents shortly in the newborns but lost in adulthood, is one of the therapeutic options for myocardial repair post various insults. In this work, we performed the phosphoproteomic analysis on neonatal regenerative myocardium and explored the Kinase-substrate network in neonatal myocardium to define potential signaling, which might be responsible for the transient regenerative capacity in the newborn mice.

2020-02-28 | PXD014865 | Pride

Ketogenic diet exerted anti-seizure function related with alteration of lipid metabolism via pparγ signaling pathway

Project description:The ketogenic diet (KD) is an established therapy for drug-resistant epilepsy, yet its precise anticonvulsant mechanisms, particularly those linked to its fundamental alteration of lipid metabolism, remain incompletely understood. This study investigated the role of lipid metabolism modulation in the antiseizure effects of KD using a kainic acid (KA)-induced chronic epilepsy mouse model. Mice maintained on KD exhibited significantly reduced seizure frequency, duration, and severity, alongside decreased electrographic spike discharges and neuronal c-Fos expression compared to those on a chow diet (CD). Transcriptomic analysis of temporal lobe tissue revealed several differentially expressed genes (DEGs) in KD-fed mice, with parts identified as lipid metabolism-related. Further analysis and experiments demonstrated key genes and pathways releated to the regulation of KD in lipid metabolism subsquently exerted anti-seizure effects.

2026-06-11 | GSE315058 | GEO

Leukocyte gene expression predicts human temporal lobe epilepsy seizure frequency

Project description:This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE). A consecutive series of sixteen patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as < 2 seizures/month and > 2 seizures/month, respectively.

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FXR protects against neonatal sepsis via enhancing the immunosuppressive function of MDSCs

Project description:The presence of myeloid-derived suppressor cells (MDSCs) during the early postnatal period plays a protective role against neonatal inflammation. However, the mechanisms regulating neonatal MDSCs remain to be fully elucidated. In this study, we report that the bile acid receptor Farnesoid X receptor (FXR) acts as a pivotal positive regulator of neonatal MDSCs. Using FXR-deficient (FXR-/-) mice and FDA-approved FXR agonist obeticholic acid (OCA), we demonstrated that FXR deficiency impairs the immunosuppressive and antibacterial functions of neonatal MDSCs, thereby exacerbating the severity of neonatal sepsis. Adoptive transfer of MDSCs alleviates sepsis severity in FXR-/- neonatal pups. Mechanistic studies reveal that HIF1a, a well-established regulator of MDSCs, is a direct transcriptional target of FXR. Patients with neonatal sepsis displayed reduced MDSC frequencies and impaired expression of FXR and HIF-1α, which was negatively correlate with the clinical parameters. These observations highlight the important role of FXR in neonatal MDSCs and its therapeutic potential in neonatal sepsis.

2025-05-20 | GSE289598 | GEO

A spatial transcriptomic atlas of acute neonatal lung injury across development and disease severity

Project description:A spatial transcriptomic atlas of acute neonatal lung injury across development and disease severity

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CD36/FABP5/PPARδ signaling axis defines spontaneously proliferating cardiomyocytes in neonatal stages

Project description:Spontaneously cycling cardiomyocytes (CMs) represent a rare and unique population in the neonatal heart with the potential to drive cardiac regeneration in adulthood. While previous studies have observed their existence, the mechanisms regulating their cell cycle activity remain poorly understood. Here, we aim to identify the signaling axis that defines the spontaneously proliferating CMs in the neonatal stage.

2026-02-19 | GSE290000 | GEO

microRNAs profiling in hippocampal cells of mouse with Sound-induced Seizure

Project description:After an electrically induced seizure, mice (NMRI) received electrical stimulation (current intensity 44 mA, 0.2 ms monopolar pulses at 6 Hz frequency for 3 s). RNA was extracted from the hippocampi at 0, 3, 6, 24 and 72 h after the seizure. microRNA expressions were measured via microarray technology using Exiqon's miCURY™ LNA Arrays. Time-course design, treated cells at 0, 3, 6, 24, and 72 h, with 7 replicate each

2014-01-01 | E-GEOD-51840 | biostudies-arrayexpress

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