Hyper-hippocampal glycogen induced by glycogen loading with exhaustive exercise

Abstract

Glycogen loading (GL), a well-known type of sports conditioning, in combination with exercise and a high carbohydrate diet (HCD) for 1 week enhances individual endurance capacity through muscle glycogen supercompensation. This exercise-diet combination is necessary for successful GL. Glycogen in the brain contributes to hippocampus-related memory functions and endurance capacity. Although the effect of HCD on the brain remains unknown, brain supercompensation occurs following exhaustive exercise (EE), a component of GL. We thus employed a rat model of GL and examined whether GL increases glycogen levels in the brain as well as in muscle, and found that GL increased glycogen levels in the hippocampus and hypothalamus, as well as in muscle. We further explored the essential components of GL (exercise and/or diet conditions) to establish a minimal model of GL focusing on the brain. Exercise, rather than a HCD, was found to be crucial for GL-induced hyper-glycogen in muscle, the hippocampus and the hypothalamus. Moreover, EE was essential for hyper-glycogen only in the hippocampus even without HCD. Here we propose the EE component of GL without HCD as a condition that enhances brain glycogen stores especially in the hippocampus, implicating a physiological strategy to enhance hippocampal functions.

Figure 1

Experimental design. (A) One-week GL protocol for rat model (Experiment 1). Rats were divided into a Pre-GL and a Post-GL group, and underwent GL protocols with HCD (70% carbohydrates) and EX (day 1: exhaustive exercise (20 m/min until exhaustion), days 2–4: moderate exercise (20 m/min, 30 min/day), days 5–7: sedentary (rest on treadmill, 30 min/day)). Rats were sacrificed using high-power microwave irradiation (10 kW, 1.2 sec). (B) GL protocol to investigate the importance of the HCD component during GL (Experiment 2). Rats were divided into three diet groups each with different amount of carbohydrate (low: 5%, middle: 35%, and high: 70%) and fixed EX. Each group underwent GL protocol. (C) GL protocol to investigate the importance of the EX component during GL (Experiment 3). Rats were divided into two groups (HCD + EX and HCD + Sed), and underwent GL protocol. (D) GL with conventional-diet protocol to investigate the essential exercise condition during GL (Experiment 4). Rats were divided into four exercise groups (EE + Mod, a combination of exhaustive exercise and moderate exercise; EE, exhaustive exercise alone; Mod, moderate exercise alone; and Sed, sedentary), and underwent GL with a conventional diet (61% carbohydrates).

Figure 2

GL increased glycogen levels in muscle and the brains. (A) Experimental design. (B) Glycogen levels in the whole brain, muscle, and liver for pre- and post-GL. (C) Glycogen levels in the five brain loci (hippocampus, cerebellum, brainstem cortex and hypothalamus). Data are expressed as mean ± standard error (n = 6–8/group). *P < 0.05; **P < 0.01 versus pre-GL group (unpaired t test).

Figure 3

GL-induced hyper-glycogen in the muscle, but not in brain, is associated with carbohydrate intake. (A) Experimental design. (B) Glycogen levels in muscle, liver, and brain (hippocampus, hypothalamus, and cortex). Data are expressed as mean ± standard error (n = 7–8/group) **P < 0.01 versus 5% group (Dunnett’s post hoc test). (C) Correlation between carbohydrate intake and glycogen levels in muscle, liver, hippocampus, hypothalamus and cortex. Data are expressed as mean ± standard error (n = 7–8/group). Correlations are shown between the carbohydrate intake and glycogen levels. Lines in the scatter plots show significant correlation (by Pearson’s product-moment correlations test).

Figure 4

EX during GL is required for GL-induced hyper-glycogen in the muscle and the brain. (A) Experimental design. (B) Muscle glycogen. (C) Liver glycogen. (D) Brain glycogen levels in hippocampus, hypothalamus, and cortex. Data are expressed as mean ± standard error (n = 4–5/group) *P < 0.05; **P < 0.01 versus HCD ± Sed group (unpaired t test).

Figure 5

Exhaustive, but not moderate, exercise in GL icreasesd hippocampal glycogen with conventional diet. (A) Experimental design. (B) Muscle glycogen. (C) Liver glycogen. (D) Hippocampal, hypothalamic and cortical glycogen. Data are expressed as mean ± standard error (n = 5–10/group). *P < 0.05; **P < 0.01 versus sedentary group (Dunnett’s post hoc test).