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Microglia Mitochondria Support Neuronal Maturation via Metabolic and Transcriptional Reprogramming in Human 3D In Vitro Brain Model.

Overview

Authors: Sydney P Sterben1, Charitha C Anamala1, Sahan B S Kansakar1, Vaishnavi Koduri1, Volha Liaudanskaya1,2
  1. Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA
  2. Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
Institutions: University of Cincinnati (United States)
Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany), volume 13, issue 25, article e08815
Dates: received 16 May 2025; accepted 13 February 2026; published online 13 March 2026; in print May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/advs.202508815 · PMID 41823577 · PMCID PMC13137835 · OpenAlex W7135199028
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), autism (population)
Methods: Spectral & time-frequency, Statistics, Connectivity
Keywords: autism spectrum disorder, microglia, mitochondria, neurodevelopment, transcriptional reprogramming
MeSH: Autism Spectrum Disorder*, Brain*, Microglia*, Mitochondria*, Neurogenesis*, Neurons*, Humans, Metabolic Reprogramming, Neurodevelopment (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: Uniformed Services University of the Health Sciences (HU00012420075); University of Cincinnati (UniversityResearchCouncilFacultyScholarsResearchAward); National Institute on Aging (1R21AG085052‐01A1); NIA NIH HHS (R21 AG085052, 1R21AG085052-01A1)
Citations: cited by 1 paper (Europe PMC); 57 references in the paper

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by disrupted neuronal circuit maturation. Emerging evidence implicates microglial function and mitochondrial regulation as contributors to ASD‐associated biology, yet the mechanisms linking these processes to neuronal development remain poorly defined. Neuronal maturation requires tightly coordinated metabolic and transcriptional remodeling, in which mitochondria play a central role in regulating the developmental tempo and metabolic identity, while microglia modulate neuronal synaptic network maturation; however, whether microglia influence neuronal development through direct mitochondrial contributions remains unknown. Here, using a 3D human in vitro brain model, it is shown that microglial mitochondria can act as transferable cues that promote metabolic, mitochondria‐dynamic, and transcriptional aspects of neuronal maturation. Neurons treated with microglial mitochondria exhibited enhanced oxidative metabolism, improved mitochondrial dynamics, and activation of gene programs associated with nervous system development and neurogenesis. These effects are accompanied by increased expression of dendritic maturation markers, supporting the view that transferred mitochondria can contribute to the regulation of neuronal state. However, full structural and synaptic maturation required the combined action of microglia‐derived mitochondria and secreted signaling factors. Together, this study identified microglial mitochondrial transfer as a contributor to neuronal maturation with potential relevance to developmental trajectories disrupted in ASD.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data Availability Statement

All data generated or analyzed during this study are included in this article (and its supporting information files). This study's mRNA sequencing data set was deposited in the GEO repository database (https://www.ncbi.nlm.nih.gov/geo/) with accession number GSE319314 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319314).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 5 keywords, 9 MeSH terms, 4 funders, 56 references.

Cite

This paper

Sterben, S. P., Anamala, C. C., Kansakar, S. B. S., Koduri, V., & Liaudanskaya, V. (2026). Microglia Mitochondria Support Neuronal Maturation via Metabolic and Transcriptional Reprogramming in Human 3D In Vitro Brain Model. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(25), e08815. https://doi.org/10.1002/advs.202508815

BibTeX

@article{sterben2026microglia,
author = {Sterben, Sydney P and Anamala, Charitha C and Kansakar, Sahan B S and Koduri, Vaishnavi and Liaudanskaya, Volha},
title = {{Microglia Mitochondria Support Neuronal Maturation via Metabolic and Transcriptional Reprogramming in Human 3D In Vitro Brain Model}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = mar,
volume = {13},
number = {25},
pages = {e08815},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/advs.202508815},
url = {https://doi.org/10.1002/advs.202508815},
pmid = {41823577},
pmcid = {PMC13137835}
}

RIS

TY - JOUR
AU - Sterben, Sydney P
AU - Anamala, Charitha C
AU - Kansakar, Sahan B S
AU - Koduri, Vaishnavi
AU - Liaudanskaya, Volha
TI - Microglia Mitochondria Support Neuronal Maturation via Metabolic and Transcriptional Reprogramming in Human 3D In Vitro Brain Model
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/03/13
VL - 13
IS - 25
SP - e08815
SN - 2198-3844
PB - Wiley
DO - 10.1002/advs.202508815
UR - https://doi.org/10.1002/advs.202508815
LA - en
ER -

CSL-JSON

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