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Updated: May 11, 2026
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Culturing Microglia from the Neonatal and Adult Central Nervous System
Published on: August 9, 2013
Activated microglia enhance neurogenesis via trypsinogen secretion
Angeliki M Nikolakopoulou1, Ranjan Dutta, Zhihong Chen
1Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Summary
Activated microglia promote neurogenesis by secreting protease serine 2 (PRSS2). This finding offers insights into potential therapeutic strategies for central nervous system repair and regeneration in conditions like multiple sclerosis.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Multiple sclerosis (MS) involves demyelination and destruction of white matter neurons.
- Activated microglia are present in chronic MS lesions, suggesting a role in tissue repair.
- The potential for neurogenesis from white matter cells in MS remains an area of investigation.
Purpose of the Study:
- To determine if activated microglia secrete factors that promote neurogenesis from white matter cells.
- To identify specific factors involved in microglia-mediated neurogenesis.
- To explore the cellular origins of newly generated neurons in response to microglia activation.
Main Methods:
- Isolation and co-culture of adult rat microglia (resting and activated) with neonatal rat optic nerve cells.
- Flow cytometry and neuron-specific class III beta-tubulin (TUJ-1) labeling to identify neuronal cells.
- Mass spectrometry to identify secreted factors from microglia and functional assays with identified factors and inhibitors.
Main Results:
- Co-culture with activated microglia significantly increased the number of TUJ-1-positive neuronal cells compared to resting microglia.
- A2B5-negative cells were the primary source (∼70%) of new neurons, with A2B5-positive oligodendrocyte progenitor cells contributing ~30%.
- Protease serine 2 (PRSS2) was identified as a key factor secreted by activated microglia that promotes neurogenesis.
Conclusions:
- Activated microglia enhance neurogenesis in white matter cell cultures.
- The neurogenic effect is mediated, in part, by the secreted factor PRSS2.
- These findings suggest a potential mechanism for endogenous repair in the central nervous system and therapeutic targets for neurodegenerative diseases.
