| First Author | Britz J | Year | 2024 |
| Journal | J Alzheimers Dis | Volume | 97 |
| Issue | 2 | Pages | 855-870 |
| PubMed ID | 38143343 | Mgi Jnum | J:359066 |
| Mgi Id | MGI:7782771 | Doi | 10.3233/JAD-230089 |
| Citation | Britz J, et al. (2024) Sex-Dependent Effects of Chronic Circadian Disruption in AbetaPP/PS1 Mice. J Alzheimers Dis 97(2):855-870 |
| abstractText | BACKGROUND: Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects. OBJECTIVE: The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AbetaPP/PS1 mouse model of Alzheimer's disease (AD). METHODS: A chronic CD was imposed until animals reached 6 or 12 months of age in AbetaPP/PS1 and C57BL/6J control mice. Home cage activity was monitored for a period of 3-4 weeks prior to the endpoint along with a single timepoint measure of glucose sensitivity. To assess long term effects of CD on the AD phenotype, animals were re-entrained to a no disruption (ND) schedule just prior to the endpoint, after which a Morris water maze (MWM) was used to assess spatial learning and memory. RESULTS: Dampening of nighttime activity levels occurred in disrupted animals, and female animals demonstrated a greater adaptability to CD. Diminished arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) levels in the suprachiasmatic nucleus (SCN) of 12-month male AbetaPP/PS1 exposed to the CD paradigm were observed, potentially accounting for the diminished re-entrainment response. Similarly, CD worsened performance in the MWM in 12-month male AbetaPP/PS1 animals, whereas no effect was seen in females. CONCLUSIONS: Collectively, these findings show that exposure to chronic CD impairs circadian behavioral patterns and cognitive phenotypes of AbetaPP/PS1 mouse model in a sex-dependent manner. |
