<p>Beneficial effects of resveratrol and exercise training on cardiac and aortic function and structure in the 3xTg mouse model of Alzheimer&rsquo;s disease</p>

Abstract

Background: Studies have indicated an association between Alzheimer’s disease (AD) and increased risk of developing cardiovascular complications. Lifestyle modifiable factors, such as exercise and diet, are known to prevent cardio-cerebral disease. Recent studies demonstrate that hearts from early onset triple-transgenic AD mice exhibit pathologies, but it is not clear whether cardiovascular function is altered in this model. Methods: In this study, we measured in vivo cardiovascular function in 7-month-old male 3xTg mice and age-matched wild-type (WT) mice using high-frequency high-resolution ultrasound imaging. Results: Our findings indicated that aortic root measurements and interventricular septal dimensions were similar in 3xTg and wild-type mice. Systolic function, expressed as ejection fraction and fractional shortening, were decreased in 3xTg mice. Late (A) ventricular filling velocities, the early/atrial (E/A) ratio, and mitral valve deceleration time, all indices of diastolic function, were increased in 3xTg mice compared to WT mice. Treadmill exercise training and resveratrol supplementation in the diet for 5 months improved ejection fraction, fractional shortening, and restored diastolic deceleration times. Pulse wave velocity was ~33% higher in 3xTg, and accompanied by a significant increase in elastin fiber fragmentation within the aortic wall, which was associated with decrease in elastin content and fiber length. Aortic wall and adventitia thickness were increased in 3xTg mice compared to the WT group. Exercise training and resveratrol supplementation, or both, improved overall aortic morphology with no change in pulse wave velocity. Conclusion: Taken together, the results indicate that the aberrations in cardiac function and aortic elastin morphology observed in the 3xTg mouse model of AD can be prevented with exercise training and treatment with resveratrol. The benefits of regular exercise training and resveratrol supplementation of heart and aortic structure in the 3xTg mouse support the value of healthy lifestyle factors on cardiovascular health.

Neuroprotective Effects of Chronic Resveratrol Treatment and Exercise Training in the 3xTg-AD Mouse Model of Alzheimer’s Disease

“…In addition, no signs of poor health or distress were observed in mice treated with Resv. This was confirmed by the observation that there were no differences in food intake expressed in g/kg/day (T, 0.114 ± 0.001; 3xTg-AD, 0.126 ± 0.008; 3xTg-AD + ET, 0.120 ± 0.009; 3xTg-AD + Resv, 0.117 ± 0.007; 3xTg-AD + Resv + ET, 0.136 ± 0.007; F = 1.8738, p = 0.1544) and body weight between groups recorded at the end of the treatment protocol (range 35 ± 2 to 39 ± 2 g, NS) [ 34 ]. Based on the composition of the diet, Resv intake was estimated at 0.481 g/kg/24-h and 0.557 g/kg/24-h in 3xTg-AD mice + Resv and 3xTg-AD + Resv + ET mice, respectively.…”

“…Mice were first acclimated to daily 10-min exercise sessions at 10m/min for a period of two weeks. After this period of acclimation, training consisted of the following as described earlier [ 34 ]: week 1, 20 min at 10 m/min; week 2, 30 min at 12 m/min. At week 3, the duration was increased to 45 min and intensity to 15 m/minute corresponding to ~80% maximal oxygen-carrying capacity based on treadmill belt speed [ 102 ].…”

“…Resv (synthetic, 99% Lallilab Inc. Durham, NC, USA) was incorporated into food pellets (Dyets Inc. Bethlehem, PA, USA, Dyet #102270, modified AIN-93G purified rodent diet with 4 g/kg resveratrol). This diet was selected based on earlier studies showing cardioprotective, anti-inflammatory, and neuroprotective effects without any negative effects [ 34 , 103 , 104 ]. Mice in the WT, AD-3xTg, and 3xTg-AD + ET groups received the same purified diet without the addition of Resv.…”

“…The effects of Resv treatment in combination with chronic ET, both of which can afford neuroprotection have not been well characterized in the 3xTg mouse model of AD. Recent reports have demonstrated that combined Resv and ET treatment have the advantage of improving both cardiovascular function and fracture resistance in the 3xTg mouse [ 34 , 35 ], suggesting that benefits of such treatment may also occur in other tissues, including the brains of these mice. Therefore, considering the benefits of both ET and the consumption of Resv in the prevention of neurodegenerative diseases, the purpose of this study was to examine the role of ET and dietary supplementation with Resv on different conformational toxic species of Aβ, Aβ-induced apoptosis, inflammation, neuroprotection, and regulation of the endolysosomal pathway in the 3xTg mouse.…”

HuangqiGuizhiWuwu Decoction Prevents Vascular Dysfunction in Diabetes via Inhibition of Endothelial Arginase 1

“…Blood glucose and body weight levels of each animal were measured at the first day, second, eighth, and tenth weeks of STZ injection. Both hemodynamic function and vascular wall function were assessed by ultrasound as previously described (Bhatta et al, 2015;Kenwright et al, 2015;Faita et al, 2018;Esfandiarei et al, 2019). Vascular endothelial function was measured by myograph as previously described (Yao et al, 2013).…”