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

Abstract

Central nervous system (CNS) pericytes play crucial roles in vascular development and blood–brain barrier maturation during prenatal development, as well as in regulating cerebral blood flow in adults. They have also been implicated in the pathogenesis of numerous neurological disorders. However, the behavior of pericytes in the adult brain after injury remains poorly understood, partly due to limitations in existing pericyte ablation models. To investigate pericyte responses following acute ablation and characterize a novel rodent model for pericyte research, we developed a tamoxifen-inducible PDGFRβ⁺ cell ablation model by crossing PDGFRβ-P2A-CreER^T2 and Rosa26-DTA176 transgenic mouse lines. Using this model, we studied the effects of different tamoxifen doses and conducted histological examinations 15 and 60 days post-injection to assess the impacts of PDGFRβ⁺ cell ablation in both acute and chronic phases, respectively. Our results demonstrate that 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. Additionally, we found that 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. Importantly, we observed that both pericyte coverage and numbers increased in the weeks following acute ablation, indicating the regenerative capacity of CNS pericytes in vivo. 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.