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Updated: May 27, 2025
Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Partial microglial depletion through inhibition of colony-stimulating factor 1 receptor improves synaptic plasticity
Luisa Strackeljan1, David Baidoe-Ansah1, Hadi Mirzapourdelavar1
1Molecular Neuroplasticity, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Abstract:
Microglia depletion, followed by repopulation, improves cognitive functions in the aged mouse brain. However, even temporal ablation of microglia puts the brain at a high risk of infection. Hence, in the present work, we studied if the partial reduction of microglia with PLX3397 (pexidartinib), an inhibitor of the colony-stimulating factor 1 receptor (CSF1R), could bring similar benefits as reported for microglia ablation. Aged (two-years-old) mice were treated with PLX3397 for a total of 6 weeks, which reduced microglia numbers in the hippocampus and retrosplenial cortex (RSC) to the levels seen in young mice and resulted in layer-specific ablation in the expression of microglial complement protein C1q mediating synaptic remodeling. This treatment boosted long-term potentiation in the CA1 region and improved performance in the hippocampus-dependent novel object location recognition task. Although PLX3397 treatment did not alter the number or total intensity of Wisteria floribunda agglutinin-positive perineuronal nets (PNNs) in the CA1 region of the hippocampus, it changed the fine structure of PNNs. It also elevated the expression of perisynaptic proteoglycan brevican, presynaptic vGluT1 at excitatory synapses, and vGAT in inhibitory ones in the CA1 stratum radiatum. Thus, targeting the CSF1R may provide a safe and efficient strategy to boost synaptic and cognitive functions in the aged brain.
Insights
Partial reduction of microglia using PLX3397 (CSF1R inhibitor) in aged mice improved cognitive functions and synaptic plasticity without complete depletion, offering a safer strategy for brain health.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Microglia depletion enhances cognitive function in aged mice but carries infection risks.
- Colony-stimulating factor 1 receptor (CSF1R) inhibitors offer a potential method for partial microglia modulation.
Purpose of the Study:
- To investigate if partial microglia reduction with PLX3397 (pexidartinib) can improve cognitive functions in aged mice.
- To assess the impact of CSF1R inhibition on synaptic remodeling and plasticity in the aging hippocampus.
Main Methods:
- Aged mice were treated with PLX3397 for 6 weeks to partially reduce microglia.
- Microglia numbers, C1q expression, synaptic markers, and performance in cognitive tasks were analyzed.
Main Results:
- PLX3397 treatment reduced microglia to young levels in the hippocampus and retrosplenial cortex.
- Synaptic plasticity (long-term potentiation) and hippocampus-dependent memory were enhanced.
- Changes in perineuronal net structure and increased expression of synaptic proteins (brevican, vGluT1, vGAT) were observed.
Conclusions:
- Partial microglia reduction via CSF1R inhibition is a viable strategy to improve cognitive and synaptic functions in the aged brain.
- This approach offers a safer alternative to complete microglia ablation for enhancing brain health in aging.
