Swim Training Affects on Muscle Lactate Metabolism, Nicotinamide Adenine Dinucleotides Concentration, and the Activity of NADH Shuttle Enzymes in a Mouse Model of Amyotrophic Lateral Sclerosis

<p><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">In this study, we aim to verify whether swim training can improve lactate metabolism, NAD</span><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif">&#43;</span><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> and NADH levels, as well as modify the activity of glycolytic and NADH shuttle enzymes and monocarboxylate transporters (MCTs) in skeletal muscle of amyotrophic lateral sclerosis (ALS) mice. </span></p><p><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">ALS mice (SOD1G93A) (</span><em style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">n</em><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> &#61; 7 per group) were analyzed before the onset of ALS, at first disease symptoms (trained and untrained), and the last stage of disease (trained and untrained), and then compared with a wild-type (WT) group of mice. The blood lactate and the skeletal muscle concentration of lactate, NAD</span><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif">&#43;</span><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> and NADH, MCT1 and MCT4 protein levels, as well as lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activities in skeletal muscle were determined by fluorometric, Western blotting, liquid chromatography-MS3 spectrometry, and spectrometric methods. </span></p><p><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">In the untrained terminal ALS group, there were decreased blood lactate levels (</span><em style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">p</em><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> &lt; 0.001) and increased skeletal muscle lactate levels (</span><em style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">p</em><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> &lt; 0.05) as compared with a WT group of mice. The amount of nicotinamide adenine dinucleotides in the ALS groups were also significantly reduced as well as LDH activity and the level of MCT1. Swim training increased lactate levels in the blood (</span><em style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">p</em><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> &lt; 0.05 vs. ALS TERMINAL untrained). In addition, cytosolic MDH activity and the cMDH/LDH 2.1 ratio were significantly higher in trained vs. untrained mice (</span><em style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">p</em><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px"> &lt; 0.05). </span></p><p><span style="color:rgb( 27 , 27 , 27 );font-family:&#39;cambria&#39; , &#39;cambria math&#39; , &#39;charter&#39; , &#39;times new roman&#39; , &#39;times&#39; , &#39;stixgeneral&#39; , serif;font-size:18.6667px">The data indicate significant dysfunction of lactate metabolism in ALS mice, associated with a reduction in muscle anaerobic metabolism and NADH transporting enzymes, as well as swim-induced compensation of energy demands in the ALS mice.</span></p>