Seasonal Changes in Serum Metabolites in Multiple Sclerosis Relapse

Abstract

Multiple sclerosis (MS) is a debilitating chronic disease of unknown etiology. There are limited treatment options due to an incomplete understanding of disease pathology. The disease is shown to have seasonal exacerbation of clinical symptoms. The mechanisms of such seasonal worsening of symptoms remains unknown. In this study, we applied targeted metabolomics analysis of serum samples using LC-MC/MC to determine seasonal changes in metabolites throughout the four seasons. We also analyzed seasonal serum cytokine alterations in patients with relapsed MS. For the first time, we can demonstrate seasonal changes in various metabolites in MS compared to the control. More metabolites were affected in MS in the fall season followed by spring, while summer MS was characterized by the smallest number of affected metabolites. Ceramides were activated in all seasons, suggesting their central role in the disease pathogenesis. Substantial changes in glucose metabolite levels were found in MS, indicating a potential shift to glycolysis. An increased serum level of quinolinic acid was demonstrated in winter MS. Histidine pathways were affected, suggesting their role in relapse of MS in the spring and fall. We also found that spring and fall seasons had a higher number of overlapping metabolites affected in MS. This could be explained by patients having a relapse of symptoms during these two seasons.

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“…In the spring, two groups of metabolites are present. 85 One contains two pathways (phosphatidylethanolamine biosynthesis and phosphatidylcholine biosynthesis), and the other six pathways (beta-alanine, histidine, ammonia recycling, methionine, glutamate, purine). 85 During summer, the first group was identical, and the second one had six metabolites (gluconeogenesis, pyruvate, urea cycle, glutamate, aspartate, and purine) different.…”

“… 85 One contains two pathways (phosphatidylethanolamine biosynthesis and phosphatidylcholine biosynthesis), and the other six pathways (beta-alanine, histidine, ammonia recycling, methionine, glutamate, purine). 85 During summer, the first group was identical, and the second one had six metabolites (gluconeogenesis, pyruvate, urea cycle, glutamate, aspartate, and purine) different. 85 Histidine, beta-alanine and methyl histidine metabolism are active in spring and fall in MS, where histidine and beta-alanine metabolism, methyl histidine metabolism the pathway was the most affected in MS. 85 Lower levels of metabolites of the glucose metabolism pathway in MS explain reports of lower glucose levels in MS. 85 Warburg effect in fall and winter MS serum refers to increased glycolysis and fermentation of pyruvate to lactate as an alternative to oxidation in the mitochondria.…”

“… 85 During summer, the first group was identical, and the second one had six metabolites (gluconeogenesis, pyruvate, urea cycle, glutamate, aspartate, and purine) different. 85 Histidine, beta-alanine and methyl histidine metabolism are active in spring and fall in MS, where histidine and beta-alanine metabolism, methyl histidine metabolism the pathway was the most affected in MS. 85 Lower levels of metabolites of the glucose metabolism pathway in MS explain reports of lower glucose levels in MS. 85 Warburg effect in fall and winter MS serum refers to increased glycolysis and fermentation of pyruvate to lactate as an alternative to oxidation in the mitochondria. 86 1,2-13C2-Glucose tracing assesses metabolic alterations of human monocytes under neuroinflammatory conditions.…”

Circular RNAs: A New Approach to Multiple Sclerosis

“…Moreover, research focused on the function of vitamin D and its derivatives in the etiology of MS, and it was discovered that the only season in which the amount of vitD was not higher than in control was fall: vit D serum levels were shown to be lower in the winter, spring, and summer. Globally, it can be stated which more overlapping metabolites were impacted in MS during the spring and fall seasons, and a return of symptoms during these two seasons could be explained by this fact [13].…”

Fuzzy Logic System for Classifying Multiple Sclerosis Patients as High, Medium, or Low Responders to Interferon-Beta

“…Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) [1]. Although MS can take several different forms, the most common type is relapsing-remitting MS (RRMS), characterized by alternating periods of remission and intensification of symptoms [2]. The etiology of MS can include several factors, such as genetic susceptibility and viral infections [3][4][5], which activate the immune system, generating immune dysregulation, and producing an immune attack against the myelin covering of the CNS [6].…”