[논문]Both endurance- and resistance-type exercise prevents neurodegeneration and cognitive decline in mice with impaired glucose tolerance

Woo, Jinhee; Shin, Ki-Ok; Park, Chan-Ho; Yoon, Byung-Kon; Kim, Do-Yeon; Bae, Ju-Yong; Lee, Yul-Hyo; Ko, Kangeun; Roh, Hee-Tae

doi:10.12925/jkocs.2019.36.3.804

Both endurance- and resistance-type exercise prevents neurodegeneration and cognitive decline in mice with impaired glucose tolerance 원문보기

Journal of the Korean Applied Science and Technology = 한국응용과학기술학회지, v.36 no.3, 2019년, pp.804 - 812

Woo, Jinhee (Department of Physical Education, College of Arts and Physical Education, Dong-A University) , Shin, Ki-Ok (Department of Physical Education, College of Arts and Physical Education, Dong-A University) , Park, Chan-Ho (Department of Leisure and Sport, Dong-Eui University) , Yoon, Byung-Kon (Department of Physical Education, Dong-Eui University) , Kim, Do-Yeon (Department of Physical Education, Pusan National University) , Bae, Ju-Yong (Department of Physical Education, College of Arts and Physical Education, Dong-A University) , Lee, Yul-Hyo (Department of Physical Education, College of Arts and Physical Education, Dong-A University) , Ko, Kangeun (Department of Physical Education, College of Arts and Physical Education, Dong-A University) , Roh, Hee-Tae (Department of Physical Education, College of Arts and Physical Education, Dong-A University)

Abstract ▼ AI-Helper

The purpose of this study was to investigate the effects of different types of exercise training on neurodegeneration and cognitive function in mice with impaired glucose tolerance (IGT). Thirty-six male C57BL/6 mice were randomly assigned to the control (CO, n = 9) and impaired glucose tolerance (IGT, n = 27) groups. The IGT group consumed 45% high fat diet for 4 weeks and received 40 mg/kg of streptozotocin twice in the lower abdomen to induce IGT. After the IGT induction period, the IGT group was subdivided into IGT + sedentary (IGT, n = 9), IGT + endurance exercise (IGTE, n = 9), and IGT + resistance exercise (IGTR, n = 9). The IGTE and IGTR groups performed treadmill and ladder climbing exercises 5 times per week for 8 weeks, respectively. Fasting glucose and glycated hemoglobin (HbA1c) levels were significantly higher in IGT group than in CO, IGTE, and IGTR groups (p < 0.05). HOMA-IR was significantly higher in IGT group than CO group (p < 0.05). Hippocampal catalase (CAT) was significantly lower in IGT group than in CO group (p < 0.05), while beta-amyloid ($A{\beta}$) was significantly higher in IGT group than in CO group (p < 0.05). Hippocampal tau was significantly higher in IGT group than in CO, IGTE, and IGTR groups (p < 0.05). The Y-maze test performance for cognitive function was significantly lower in IGT group than in CO, IGTE, and IGTR groups (p <0.05). These results suggest that IGT induces neurodegeneration and negatively affects cognitive function, while regular exercise may be effective in alleviating neurodegeneration and cognitive decline regardless of exercise type.

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표/그림 (3)

그림 Fig. 1. The glycemic control related parameters for the four groups after intervention.
그림 Fig. 2. The CAT and neurodegeneration related parameters for the four groups after intervention.
그림 Fig. 3. The cognitive function for the four groups after intervention.

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문제 정의

However, most previous studies reported that such findings were limited due to a focus on aerobic exercise, while others have been limited in investigating prediabetic models to identify independent effects of exercise, despite previous reports suggesting the presence of impaired neurocognitive function in pre-diabetes, such as impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). Therefore, the purpose of this study was to verify the effects of different exercise types on neurodegeneration and cognitive function in a mouse model of IGT.

제안 방법

In this study, Aβ and tau protein in the hippocampus were analyzed to verify variables related to neurodegeneration and changes in cognitive ability according to IGT and different types of exercise, followed by the Y-maze test.
In particular, T2DM occurs over a long prodromal stage, representatively in IFG and/or IGT; thus, active glycemic control through exercise intervention during this stage can be an important strategy to prevent T2DM [14,17]. In this study, glucose, glycated hemoglobin (HbA1c), and insulin levels were analyzed and homeostasis model assessment estimate of insulin resistance (HOMA-IR) was measured to verify changes in variables related to glycemic control according to IGT and different exercise type. According to our results, the IGTE and IGTR groups exhibited significantly lower glucose and HbA1c levels compared with the IGT group.
Brain tissue has many neurons and contains high levels of unsaturated fatty acids that can easily be oxidized, and, with a weak anti-oxidation defense system and high concentration of non-heme iron that acts as catalyst for the production of ROS, the brain is easily exposed to OS in disease(s) involving high blood glucose levels such as diabetes [22]. In this study, levels of the antioxidant enzyme CAT in the hippocampus were measured to verify the antioxidant status of the brain according to IGT and different types of exercise. The results revealed significantly higher levels in the IGT group compared with the CO group, although there was no significant difference according to exercise type.
25% fat) for 4 weeks. Mice with IGT were divided into the following groups at 37 weeks of age: IGT + sedentary (IGT [n = 9], not subjected to an exercise program); and IGT + endurance exercise (IGTE [n = 9]), and IGT + resistance exercise (IGTR [n = 9], which were subjected to 8-week endurance exercise and resistance exercise programs, respectively. The IGTE group was subjected to treadmill running for 40 min/day, 5 days/week, for 8 weeks.
Mice with IGT were divided into the following groups at 37 weeks of age: IGT + sedentary (IGT [n = 9], not subjected to an exercise program); and IGT + endurance exercise (IGTE [n = 9]), and IGT + resistance exercise (IGTR [n = 9], which were subjected to 8-week endurance exercise and resistance exercise programs, respectively. The IGTE group was subjected to treadmill running for 40 min/day, 5 days/week, for 8 weeks. For warm-up and warm-down exercise, the mice ran for 5 min at 5 m/min, while the main exercise of 30 min was running at 8 m/min for 1–4 weeks, followed by gradual increase from 8 m/min to 10 m/min for 5–8 weeks.
The glucose level was estimated using a GlucoDr glucometer (Allmedicus, Korea). The analysis of glycated hemoglobin (HbA1c) and insulin levels were carried out using an ELISA kit for glycated hemoglobin A1c (CEA190Mu, Cloud-Clone Corp., China) and an ELISA kit for insulin (CEA448Mu, Cloud-Clone Corp., China), respectively. Insulin resistance index was assessed by homeostasis model assessment estimate of insulin resistance (HOMA-IR) as follows: HOMA-IR = Fasting insulin (μ IU/mL) × Fasting glucose (mg/dL) / 405.

대상 데이터

Four-week-old C57BL/6 mice were used in this study. Four mice were housed per cage in the Dong-A University College of Medicine Animal Laboratory. The laboratory conditions were maintained constant: 55% relative humidity, 22 ± 2 ℃, and a 12-h dark–light cycle.
Four-week-old C57BL/6 mice were used in this study. Four mice were housed per cage in the Dong-A University College of Medicine Animal Laboratory.

데이터처리

, USA), and all measurements were presented as the means ± standard error (SE). One-way ANOVA was used to verify the inter-group differences in the blood components and the results of tissue analysis. When statistical significance was evident, Tukey's post-hoc analysis was carried out.

이론/모형

Cognitive function was assessed using the Y-maze test. The Y-maze consists of three arms and each arm (5 cm wide, 35 cm length, and 10 cm height) was designated as A, B, and C, respectively.

성능/효과

In this study, glucose, glycated hemoglobin (HbA1c), and insulin levels were analyzed and homeostasis model assessment estimate of insulin resistance (HOMA-IR) was measured to verify changes in variables related to glycemic control according to IGT and different exercise type. According to our results, the IGTE and IGTR groups exhibited significantly lower glucose and HbA1c levels compared with the IGT group. This suggests that endurance and resistance exercise were both effective for glycemic control, and also re-confirms previous studies investigating the effectiveness of various types of exercise in lowering blood glucose and HbA1c levels in prediabetes, as well as in patients with diabetes [18,19,20].
Fasting glucose and glycated hemoglobin (HbA1c) levels were significantly higher in the IGT group than in the CO, IGTE, and IGTR groups (p < 0.05), while insulin levels were not significantly different among the groups (p > 0.05).
The results revealed significantly high Aβ levels in the hippocampus in the IGT group compared with the CO group, while tau levels were significantly lower in the CO, IGTE, and IGTR groups compared with the IGT group. Furthermore, results of the Y-maze test to evaluate cognitive function revealed significantly higher levels in the CO, IGTE, and IGTR groups compared with the IGT group. This result suggests that IGT in the pre-diabetic stage can induce neurodegeneration by the accumulation of Aβ and tau protein in the hippocampus, while endurance and resistance exercise can effectively reduce neurodegeneration and cognitive decline, in which significant decrease in glucose and HbA1c through exercise may act as important factors.
Hippocampal CAT was significantly lower in the IGT group than in the CO group (p < 0.05), while beta-amyloid (Aβ) was significantly higher in the IGT group than in the CO group (p < 0.05).
In addition, homeostasis model assessment estimate of insulin resistance (HOMA-IR) was significantly higher in the IGT group than in the CO group (p < 0.05).
In conclusion, impaired glucose tolerance (IGT) induces neurodegeneration and negatively affects cognitive function, while regular exercise may be effective in alleviating neurodegeneration and cognitive decline regardless of exercise type. In future studies, it is necessary to develop an exercise program to prevent progression to type 2 diabetes at high risk stages such as IGT by applying various exercise intensity and/or exercise volumes as well as exercise type.
The results revealed significantly high Aβ levels in the hippocampus in the IGT group compared with the CO group, while tau levels were significantly lower in the CO, IGTE, and IGTR groups compared with the IGT group.
In this study, levels of the antioxidant enzyme CAT in the hippocampus were measured to verify the antioxidant status of the brain according to IGT and different types of exercise. The results revealed significantly higher levels in the IGT group compared with the CO group, although there was no significant difference according to exercise type. This result suggests that high glucose levels due to IGT negatively affected antioxidant capacity.
Y-maze test performance was significantly lower in the IGT group than in the CO, IGTE, and IGTR groups (p < 0.05).

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