Effects of Long-Term Endurance Exercise and Lithium Treatment on Neuroprotective Factors in Hippocampus of Obese Rats

Abstract

To investigate the effects of long-term lithium treatment and low intensity endurance exercise on brain-derived neurotrophic factor (BDNF) expression and glycogen synthase kinase 3 beta (GSK3β) activity in the hippocampus of obese rats. Fifty 10-week-old male Sprague-Dawley rats were selected. There was a control group of 10 rats (chow control group) while the other forty rats were fed on a high-fat diet for eight weeks to induce obesity. Rats were then assigned into four random groups. The rats were given 10 mg/kg lithium chloride (LiCl) dissolved in 1 mL sterile distilled water once a day, 5 times a week. The rats did 20 min of treadmill walking with an exercise intensity of 40% maximal oxygen uptake (VO₂ max) (12 m/min, slope 0%). This was performed for 20 min a day, 3 days a week. Twelve weeks of lithium treatment or endurance exercise significantly reduced body weight and body fat mass in obese rats, without showing additive effects when the treatments were given in parallel or significant toxic responses in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and kidney and liver tissues. BDNF expression in the hippocampus was significantly increased both in exercise and lithium groups with synergistic effects found in the group where both exercise and lithium treatments were given in parallel. On the other hand, the decrease in GSK3β activity was shown only in the lithium treatment group, without showing additive effects when the treatments were given in parallel. Lithium and low-intensity endurance exercise for 12 weeks increased the expression of BDNF, a neuroprotective factor in the hippocampus of obese mice. Lithium treatment alone inhibited the activity of GSK3β. This can be interpreted as a positive indication of applicability of the two factors in the prevention of neurodegenerative diseases.

Keywords: exercise; hippocampus; lithium; obesity.

Figure 1

Hematoxylin and eosin staining in kidney and liver tissue. (Histological changes were evaluated in nonconsecutive histological fields, randomly chosen at a magnification of 100×. Scale bar, 100 μm; black arrow indicates a normal state that cannot confirm the degeneration of the tubule in kidney).

Figure 2

Level of BDNF protein expression. a: Significantly different from CC (p < 0.05). b: Significantly different from FC (p < 0.05). c: Significantly different from Li (p < 0.05). d: Significantly different from Ex (p < 0.05).

Figure 3

GSK3β/p-GSK3β protein expression ratio. a: Significantly different from CC (p < 0.05). c: Significantly different from Li (p < 0.05). e: Significantly different from LEx (p < 0.05).