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Microglia Mitochondria Support Neuronal Maturation via Metabolic and Transcriptional Reprogramming in Human 3D In
Sydney P Sterben1, Charitha C Anamala1, Sahan B S Kansakar1
1Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 13, 2026
Summary
Microglia can transfer mitochondria to neurons, enhancing neuronal development and maturation. This microglial mitochondrial transfer offers insights into neurodevelopmental conditions like Autism Spectrum Disorder (ASD).
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Autism Spectrum Disorder (ASD) involves disrupted neuronal circuit maturation.
- Microglial function and mitochondrial regulation are implicated in ASD.
- Mechanisms linking microglia, mitochondria, and neuronal development are unclear.
Purpose of the Study:
- To investigate if microglial mitochondria influence neuronal maturation.
- To explore the role of microglial mitochondrial transfer in neuronal development.
- To understand potential links to Autism Spectrum Disorder (ASD) biology.
Main Methods:
- Utilized a 3D human in vitro brain model.
- Examined the effects of microglial mitochondria on neuronal cells.
- Analyzed metabolic, mitochondrial dynamics, and transcriptional changes in neurons.
Main Results:
- Microglial mitochondria transfer enhanced neuronal oxidative metabolism and mitochondrial dynamics.
- Transferred mitochondria activated gene programs related to neurogenesis and nervous system development.
- Dendritic maturation markers increased in neurons treated with microglial mitochondria.
- Full neuronal maturation required both mitochondrial transfer and secreted factors.
Conclusions:
- Microglial mitochondria can act as transferable cues promoting neuronal maturation.
- Mitochondrial transfer from microglia contributes to regulating neuronal state.
- This finding has potential relevance for developmental trajectories in ASD.
- Combined microglial mitochondrial transfer and signaling are crucial for complete neuronal maturation.
