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Updated: Mar 30, 2026
In Vivo Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus
Published on: July 6, 2022
Microglia regulate hippocampal neurogenesis during chronic neurodegeneration
Chiara De Lucia1, Adeline Rinchon1, Adrian Olmos-Alonso1
1Centre for Biological Sciences, University of Southampton, Southampton, United Kingdom.
Abstract:
Neurogenesis is altered in neurodegenerative disorders, partly regulated by inflammatory factors. We have investigated whether microglia, the innate immune brain cells, regulate hippocampal neurogenesis in neurodegeneration. Using the ME7 model of prion disease we applied gain- or loss-of CSF1R function, as means to stimulate or inhibit microglial proliferation, respectively, to dissect the contribution of these cells to neurogenesis. We found that increased hippocampal neurogenesis correlates with the expansion of the microglia population. The selective inhibition of microglial proliferation caused a reduction in neurogenesis and a restoration of normal neuronal differentiation, supporting a pro-neurogenic role for microglia. Using a gene screening strategy, we identified TGFβ as a molecule controlling the microglial pro-neurogenic response in chronic neurodegeneration, supported by loss-of-function mechanistic experiments. By the selective targeting of microglial proliferation we have been able to uncover a pro-neurogenic role for microglia in chronic neurodegeneration, suggesting promising therapeutic targets to normalise the neurogenic niche during neurodegeneration.
Insights
Microglia, the brain's immune cells, promote neurogenesis in neurodegenerative conditions. Inhibiting microglial proliferation reduces neurogenesis, while targeting TGFβ may offer therapeutic benefits for the neurogenic niche.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neurogenesis is impaired in neurodegenerative diseases.
- Inflammatory factors, including microglia, play a role in regulating neurogenesis.
- The specific role of microglia in neurogenesis during neurodegeneration requires further investigation.
Purpose of the Study:
- To investigate the role of microglia in regulating hippocampal neurogenesis in a model of prion disease (ME7).
- To determine if modulating microglial proliferation affects neurogenesis.
- To identify molecular mechanisms by which microglia influence neurogenesis in chronic neurodegeneration.
Main Methods:
- Utilized the ME7 mouse model of prion disease.
- Manipulated microglial proliferation using gain- or loss-of CSF1R function.
- Employed a gene screening strategy to identify key molecules.
- Conducted loss-of-function experiments to validate findings.
Main Results:
- Increased microglial proliferation correlated with enhanced hippocampal neurogenesis.
- Selective inhibition of microglial proliferation reduced neurogenesis and restored normal neuronal differentiation.
- Transforming growth factor beta (TGFβ) was identified as a key regulator of the microglial pro-neurogenic response.
Conclusions:
- Microglia possess a pro-neurogenic role in the context of chronic neurodegeneration.
- Targeting microglial proliferation represents a potential therapeutic strategy to normalize the neurogenic niche.
- TGFβ signaling is a critical mediator of microglial influence on neurogenesis during neurodegeneration.
