Longitudinal Investigation of Brain and Spinal Cord Pericytes After Inducible PDGFRβ+ Cell Ablation in Adult Mice

Journal of Neurochemistry, 2025 · DOI: https://doi.org/10.1111/jnc.70035 · Published: February 3, 2025

Cardiovascular Science Neurology Research Methodology & Design

Simple Explanation

This study created a new mouse model to study pericytes, cells important for blood vessel function in the brain and spinal cord. The model allows researchers to selectively remove pericytes at a chosen time point to see how this affects the brain and spinal cord. The researchers found that after removing pericytes, the body can regenerate them, showing the resilience of these cells. They also discovered that pericyte loss and recovery differ between the brain and spinal cord. This new model helps overcome limitations of previous models and can be used to better understand the role of pericytes in brain health and disease, such as stroke and Alzheimer's.

Study Duration

60 Days

Participants

93 mice (48 males and 45 females) aged between 8 and 16 weeks

Evidence Level

Not specified

Key Findings

1
A low dose of tamoxifen effectively ablates PDGFRβ+ cells of the CNS in mice without reducing survival or causing significant systemic side effects, such as weight loss.
2
The extent of PDGFRβ+ cell depletion varies between the cortex and the spinal cord, as well as between the gray and white matter regions of the spinal cord.
3
Pericyte coverage and numbers increased in the weeks following acute ablation, indicating the regenerative capacity of CNS pericytes in vivo.

Research Summary

The study introduces a novel tamoxifen-inducible PDGFRβ+ cell ablation model in mice to investigate pericyte responses in the CNS following acute ablation, addressing limitations in existing models. The results demonstrate that a low dose of tamoxifen effectively ablates PDGFRβ+ cells without significant side effects, and that the extent of ablation varies between different CNS regions. Importantly, the study observed the regenerative capacity of CNS pericytes, with pericyte coverage and numbers increasing in the weeks following acute ablation.

Practical Implications

Tool for Neurological Studies

This study offers a valuable tool for future studies on the role of pericytes in neurological disorders by overcoming the limitations of constitutive pericyte ablation models and providing its longitudinal characterization in the CNS.

Understanding Pericyte Regeneration

The observation of pericyte regeneration opens new avenues for research into therapies that could enhance this process to restore neurovascular function after injury or in disease.

Refined Ablation Strategies

The findings highlight the importance of dosage control and regional considerations in pericyte ablation studies, which can inform the design of more targeted and effective interventions.

Study Limitations

1
The inclusion of vSMCs and fibroblasts in the population of PDGFRβ+ cells targeted for ablation.
2
PDGFRβ+ cell ablation is not limited to the CNS, and the degree of PDGFRβ+ cell ablation can be different in other organs
3
BBB leakage, changes in glial reactivity, and inflammatory responses following induced PDGFRβ+ cell ablation in adult mice, we did not investigate these mechanisms in this study

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