The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr-/-.Leiden Mice.

Exercise and dietary interventions are promising approaches to tackle obesity and its obesogenic effects on the brain. We investigated the impact of exercise and possible synergistic effects of exercise and branched-chain amino acids (BCAA) supplementation on the brain and behavior in high-fat-diet (HFD)-induced obese Ldlr-/-.Leiden mice. Baseline measurements were performed in chow-fed Ldlr-/-.Leiden mice to assess metabolic risk factors, cognition, and brain structure using magnetic resonance imaging. Thereafter, a subgroup was sacrificed, serving as a healthy reference. The remaining mice were fed an HFD and divided into three groups: (i) no exercise, (ii) exercise, or (iii) exercise and dietary BCAA. Mice were followed for 6 months and aforementioned tests were repeated. We found that exercise alone changed cerebral blood flow, attenuated white matter loss, and reduced neuroinflammation compared to non-exercising HFD-fed mice. Contrarily, no favorable effects of exercise on the brain were found in combination with BCAA, and neuroinflammation was increased. However, cognition was slightly improved in exercising mice on BCAA. Moreover, BCAA and exercise increased the percentage of epididymal white adipose tissue and muscle weight, decreased body weight and fasting insulin levels, improved the circadian rhythm, and transiently improved grip strength. In conclusion, BCAA should be supplemented with caution, although beneficial effects on metabolism, behavior, and cognition were observed.

The Impact of Voluntary Exercise on Stroke Recovery.

Stroke treatment is limited to time-critical thrombectomy and rehabilitation by physiotherapy. Studies report beneficial effects of exercise; however, a knowledge gap exists regarding underlying mechanisms that benefit recovery of brain networks and cognition. This study aims to unravel therapeutic effects of voluntary exercise in stroke-induced mice to develop better personalized treatments. Male C57Bl6/JOlaHsd mice were subjected to transient middle cerebral artery occlusion. After surgery, the animals were divided in a voluntary exercise group with access to running wheels (RW), and a control group without running wheels (NRW). During 6 days post-stroke, activity/walking patterns were measured 24/7 in digital ventilated cages. Day 7 post-surgery, animals underwent MRI scanning (11.7T) to investigate functional connectivity (rsfMRI) and white matter (WM) integrity (DTI). Additionally, postmortem polarized light imaging (PLI) was performed to quantify WM fiber density and orientation. After MRI the animals were sacrificed and neuroinflammation and cerebral vascularisation studied. Voluntary exercise promoted myelin density recovery corresponding to higher fractional anisotropy. The deteriorating impact of stroke on WM dispersion was detected only in NRW mice. Moreover, rsfMRI revealed increased functional connectivity, cerebral blood flow and vascular quality leading to improved motor skills in the RW group. Furthermore, voluntary exercise showed immunomodulatory properties post-stroke. This study not only helped determining the therapeutic value of voluntary exercise, but also provided understanding of pathological mechanisms involved in stroke.

Automated Analysis of Stroke Mouse Trajectory Data With Traja.

Quantitative characterization of mouse activity, locomotion and walking patterns requires the monitoring of position and activity over long periods of time. Manual behavioral phenotyping, however, is time and skill-intensive, vulnerable to researcher bias and often stressful for the animals. We present examples for using a platform-independent open source trajectory analysis software, Traja, for semi-automated analysis of high throughput mouse home-cage data for neurobehavioral research. Our software quantifies numerous parameters of movement including traveled distance, velocity, turnings, and laterality which are demonstrated for application to neurobehavioral analysis. In this study, the open source software for trajectory analysis Traja is applied to movement and walking pattern observations of transient stroke induced female C57BL/6 mice (30 min middle cerebral artery occlusion) on an acute multinutrient diet intervention (Fortasyn). After stroke induction mice were single housed in Digital Ventilated Cages [DVC, GM500, Tecniplast S.p.A., Buguggiate (VA), Italy] and activity was recorded 24/7, every 250 ms using a DVC board. Significant changes in activity, velocity, and distance walked are computed with Traja. Traja identified increased walked distance and velocity in Control and Fortasyn animals over time. No diet effect was found in preference of turning direction (laterality) and distance traveled. As open source software for trajectory analysis, Traja supports independent development and validation of numerical methods and provides a useful tool for computational analysis of 24/7 mouse locomotion in home-cage environment for application in behavioral research or movement disorders.