Treatment with the mitochondrial-targeted antioxidant peptide SS -31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice methods
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Rotarod, motor skill learning
Motor coordination was assessed using the rotarod as described (Tarantini et al., ). Analysis of day-to-day changes in performance on the accelerating rotarod test was used to evaluate the motor skill learning. The grid hanging test was also used to evaluate balance and motor function. A grip strength test was used to measure the maximal muscle strength of forelimbs of the mice.
Restoration of cerebromicrovascular function is associated with improved cognitive function in aged mice treated with...
To analyze working memory function (short-term memory that is involved in immediate conscious perception), we examined re-entries into incorrect arms (without hidden platform) that were previously attempted for escape. We found that working memory function was impaired in aged mice as compared to young controls (Figure c). Aged mice that were treated with SS-31 showed significant restoration of working memory to levels comparable to young animals (Figure c). SS-31 treatment thus resulted in a marked improvement in working memory while there was no clear effect of SS-31 on learning.
EXPERIMENTAL PROCEDURES
Young (3 months, n = 30) and aged (24 months, n = 40) male C57BL/6 mice were used. Mice in the aged cohort were assigned to two groups ( n = 20 each group). One group of the aged mice was injected daily with SS-31 (elamipretide; also known as MTP-131 or Bendavia, 10 mg Kg -1 day -1, for 10 days). This dosage of SS-31 has been shown to exert potent cardioprotective effects (Dai et al., ). All procedures were approved by the Institutional Animal Use and Care Committees of the University of Oklahoma Health Sciences Center.
Statistical analysis
Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Principal component analysis, followed by MANOVA and the PCA-biplot approach were used to analyze the gait data. A p value less than.05 was considered statistically significant. Data are expressed as mean ± SEM.
Quantitative real-time RT-PCR
A quantitative real-time RT-PCR technique was used to analyze mRNA expression in cortical samples using validated TaqMan probes (Applied Biosystems) and a Strategen MX3000 platform, as previously reported (Toth, Tarantini, Ashpole et al., ).
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Gait recovery and locomotor function
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- Per-run gait capture with paw placement, timing, and stride features for each animal
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Report representative outputs alongside summary comparisons for Gait recovery and locomotor function.
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Evidence quotes (5)
Motor coordination was assessed using the rotarod as described (Tarantini et al., ). Analysis of day-to-day changes in performance on the accelerating rotarod test was used to evaluate the motor skill learning. The grid hanging test was also used to evaluate balance and motor function. A grip strength test was used to measure the maximal muscle strength of forelimbs of the mice.
To analyze working memory function (short-term memory that is involved in immediate conscious perception), we examined re-entries into incorrect arms (without hidden platform) that were previously attempted for escape. We found that working memory function was impaired in aged mice as compared to young controls (Figure c). Aged mice that were treated with SS-31 showed significant restoration of working memory to levels comparable to young animals (Figure c). SS-31 treatment thus resulted in a marked improvement in working memory while there was no clear effect of SS-31 on learning.
Young (3 months, n = 30) and aged (24 months, n = 40) male C57BL/6 mice were used. Mice in the aged cohort were assigned to two groups ( n = 20 each group). One group of the aged mice was injected daily with SS-31 (elamipretide; also known as MTP-131 or Bendavia, 10 mg Kg -1 day -1, for 10 days). This dosage of SS-31 has been shown to exert potent cardioprotective effects (Dai et al., ). All procedures were approved by the Institutional Animal Use and Care Committees of the University of Oklahoma Health Sciences Center.
Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Principal component analysis, followed by MANOVA and the PCA-biplot approach were used to analyze the gait data. A p value less than.05 was considered statistically significant. Data are expressed as mean ± SEM.
A quantitative real-time RT-PCR technique was used to analyze mRNA expression in cortical samples using validated TaqMan probes (Applied Biosystems) and a Strategen MX3000 platform, as previously reported (Toth, Tarantini, Ashpole et al., ).
Machine-readable layer
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