EFFECT OF PERICYTE ABLATION ON THE CIRCADIAN ACTIVITY PATTERNS OF MICE: A PILOT STUDY

Aim: Disruption of circadian rhythms is increasingly recognized as a critical contributor to neurological disorders; however, the cellular mechanisms linking circadian dysfunction to impaired brain clearance remain poorly understood. Pericytes have recently been shown to possess intrinsic circadian clock machinery and to regulate endothelial circadian function, yet their role in circadian regulation of the glymphatic system remains unknown. This pilot study aimed to determine whether adult pericyte ablation alters circadian locomotor activity patterns in mice.
Methods: We used a previously established tamoxifen-inducible adult PDGFRβ⁺ cell ablation mouse model (PDGFRβ-CreERT2/Rosa26-DTA176). Circadian rhythms were assessed using wheel-running–based locomotor activity recordings and actogram analyses under light–dark and constant darkness conditions.
Results: Pericyte ablation was confirmed by a 94% reduction in CD13 expression. Both control and pericyte-ablated (PA) mice maintained a stable circadian period close to 24h. However, PA mice showed increased temporal variability in rhythm power, indicating reduced circadian robustness. Core timing parameters—period, activity onset, and acrophase—were largely preserved. In contrast, controls displayed a significant post-injection amplitude increase that was absent in PA mice, leading to a reduced delta amplitude. FFT analysis confirmed a greater post-injection decrease in maximum amplitude in PA animals. The mean bouts of locomotor activity was significantly reduced after injection only in PA mice.
Conclusion: These findings indicate that pericytes are critical for maintaining circadian rhythm robustness without disrupting core circadian timing. In the next phase, perivascular AQP4 polarization, molecular clock dynamics, and glymphatic function will be examined to elucidate underlying mechanisms.