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Different Age Related Neurological and Cardiac Effects of Verapamil on a Transgenic Mouse Model of Alzheimer's
Alexandru Cojocaru1,2, Alexandra Daniela Zavaleanu1,3, Daniela Cornelia Călina4
1Department of Physiology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
Insights
Verapamil showed varied effects in Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
- Cardiology
Background:
- Dementias, particularly Alzheimer's disease (AD), represent a significant global health burden, contributing substantially to disability-adjusted life-years (DALYs).
- Limited therapeutic options exist for AD, yet patients often manage comorbidities with multiple medications.
- The increasing lifespan necessitates understanding drug interactions and effects in aging populations with AD.
Purpose of the Study:
- To investigate the neurological and cardiac effects of verapamil in a mouse model of Alzheimer's disease (AD).
- To assess potential differences in verapamil's impact based on the age of the AD model mice.
Main Methods:
- Daily administration of verapamil (3.5mg/kg) for 28 days to young and aged C57BL/6J-TgN (Thy1-APPKM670/671NL; Thy1-PS1L166P (APP) mice.
- Evaluation of behavioral changes, including anxiety and short-term memory.
- Assessment of cardiac electrophysiology, focusing on ventricular depolarization and repolarization parameters.
Main Results:
- Young APP mice exhibited reduced anxiety and improved short-term memory with minor cardiac effects (increased ventricular depolarization duration).
- Aged APP mice showed no behavioral improvements but displayed a decreased ventricular depolarization duration.
- Repolarization effects were similar across age groups, except for a prolonged ST segment duration in aged mice.
Conclusions:
- Verapamil's effects on neurological and cardiac function in this AD mouse model are age-dependent.
- The stage of Alzheimer's disease may influence the response to calcium channel blockers like verapamil.
- Clinical use of verapamil in AD patients should consider the disease stage to anticipate varied effects.
Abstract:
Dementias are the third cause of the disability-adjusted life-years (DALYs) worldwide with Alzheimer's (AD) having the highest prevalence. Despite ample research in the field, therapeutic options are limited. However, with the increase in lifespan, a larger number of AD patients will receive other medication for the evermore-increased number of comorbidities that such patients face. The purpose of this study was to evaluate the neurological and cardiac effects of verapamil, on C57BL/6J-TgN (Thy1-APPKM670/671NL; Thy1-PS1L166P (APP) mice. The daily administration of 3.5mg/kg of verapamil for 28 days revealed different effects on young and aged APP mice. While young animals showed less anxiety and improved short-term memory with minimal cardiac effects (an increase in the duration of ventricular depolarization), aged ones did not present behavioral improvements, but with a decrease in the duration of ventricular depolarizing. Repolarization effects of verapamil were similar in young and aged animals, except for the duration of the ST segment that was longer in aged animals. Considering our results, the use of calcium blockers in AD patients should take into consideration the stage of the disease, as different effects could be seen at different stages of AD, in our model.
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