Effects of exercise and alpha-lipoic acid supplementation on brain tissue protection in experimental diabetes

The present thesis aims to clarify the effects of 8 weeks of exercise training or thiol supplementation (lipoic acid, LA) on exercise-induced oxidative stress and tissue protection, including endogenous antioxidant homeostasis and heat shock proteins (HSPs) in diabetic and non-diabetic rat brain. Protection against oxidative stress, a disruption of redox control of signalling and cellular events, depends on an orchestrated synergism between several exogenous micronutrients and endogenous antioxidants. Exercise-induced oxidative stress stimulates antioxidant protection, which can also be prolonged, and may manifest a sustained response during exercise training. Physical exercise induces HSPs, which have a central role in protein homeostasis and protection in various tissues, predominantly skeletal muscle, while the effect of exercise on brain is limited.

In this study streptozotocin-induced experimental diabetes model in rat brain was used. At baseline, HSP levels, thioredoxin-1 (TRX) protein and activity and levels of thioredoxin-interacting protein (TXNip), an endogenous inhibitor of TRX were not different between SID and non-diabetic animals. Endurance training or diabetes had no effect on protein carbonyl content and other oxidative stress markers, but the proportion of oxidized glutathione (GSSG) to total GSH was increased in diabetic animals, indicating an altered redox status. The levels of elongation factor eEF-1 and eEF-2 kinase were not affected by diabetes or training.

Exercise training increased TRX protein levels in brain, but diabetes down regulated the TRX response to exercise training and induced TXNip mRNA expression. Thus, the beneficial effects of physical exercise on the TRX system were inhibited by diabetes. Similarly, endurance training increased HSP expression in brain tissue, and experimental diabetes impaired the HSP response at the protein level. Acute exhaustive exercise induced mRNA of TRX in the brain. LA supplementation did not prevent diabetes-induced disturbances in GSH and TRX homeostasis; in contrast, LA supplementation increased TXNip transcription. Moreover, LA supplementation increased HSC70 mRNA expression in diabetic animals, but decreased expression in non-diabetic controls. On the other hand, LA supplementation had no effect on the levels of any of the proteins analysed.

Based on this study, brain antioxidant status and redox regulation can be improved in a safe and physiological manner by exercise training, which may provide a means for improving brain health. However, LA supplementation had no beneficial effects on brain protection.


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City (for University):
University of Eastern Finland