The Frequency-Dependent Aerobic Exercise Effects of Hypothalamic GABAergic Expression and Cardiovascular Functions in Aged Rats

Yan Li, Ziqi Zhao, Jiajia Cai, Boya Gu, Yuanyuan Lv, Li Zhao, Yan Li, Ziqi Zhao, Jiajia Cai, Boya Gu, Yuanyuan Lv, Li Zhao

Abstract

A decline in cardiovascular modulation is a feature of the normal aging process and associated with cardiovascular diseases (CVDs) such as hypertension and stroke. Exercise training is known to promote cardiovascular adaptation in young animals and positive effects on motor and cognitive capabilities, as well as on brain plasticity for all ages in mice. Here, we examine the question of whether aerobic exercise interventions may impact the GABAergic neurons of the paraventricular nucleus (PVN) in aged rats which have been observed to have a decline in cardiovascular integration function. In the present study, young (2 months) and old (24 months) male Wistar rats were divided into young control (YC), old sedentary, old low frequency exercise (20 m/min, 60 min/day, 3 days/week, 12 weeks) and old high frequency exercise (20 m/min, 60 min/day, 5 days/week, 12 weeks). Exercise training indexes were obtained, including resting heart rate (HR), blood pressure (BP), plasma norepinephrine (NE), and heart weight (HW)-to-body weight (BW) ratios. The brain was removed and processed according to the immunofluorescence staining and western blot used to analyze the GABAergic terminal density, the proteins of GAD67, GABAA receptor and gephyrin in the PVN. There were significant changes in aged rats compared with those in the YC. Twelve weeks aerobic exercise training has volume-dependent ameliorated effects on cardiovascular parameters, autonomic nervous activities and GABAergic system functions. These data suggest that the density of GABAergic declines in the PVN is associated with imbalance in autonomic nervous activities in normal aging. Additionally, aerobic exercise can rescue aging-related an overactivity of the sympathetic nervous system and induces modifications the resting BP and HR to lower values via improving the GABAergic system in the PVN.

Keywords: GABAergic neurons; PVN; aerobic exercise; aging process; cardiovascular function.

Figures

Figure 1
Figure 1
Effects of 12 weeks of aerobic exercise on autonomic nervous system modulation. (A–C) the LF value (A), HF value (B) and LF/HF ratio (C) in young control (YC), old sedentary (O-SED), old low frequency exercise (O-LEX) and old high frequency exercise (O-HEX) group, respectively. (D) The plasma NE level in each group. *p < 0.05 vs. YC; #p < 0.05 vs. O-SED; &p < 0.05 vs. O-LEX; **p < 0.01 vs. YC; ##p < 0.01 vs. O-SED; &&p < 0.01 vs. O-LEX. n = 12 in each group.
Figure 2
Figure 2
Representative heart rate (HR) traces for each group. HR and blood pressure (BP) of animals from each group were measured using a BP-300A noninvasive tail-cuff system. The HR trace was used for a spectral analysis with BP-300A software. YC, young control group; O-SED, old sedentary group; O-LEX, old low frequency exercise group; O-HEX, old high frequency exercise group. Bar = 2 s.
Figure 3
Figure 3
Effects of 12 weeks of aerobic exercise on the number of GABAergic neurons in the paraventricular nucleus (PVN). (A) Immunofluorescence staining of GABAergic neurons (GAD67-positive) in the PVN in YC, O-SED, O-LEX and O-HEX group, respectively. (B) Number of GABAergic neurons in the PVN in YC, O-SED, O-LEX and O-HEX group. 3V, the third ventricle. Scale bar = 50 μm. **p < 0.01 vs. YC; ##p < 0.01 vs. O-SED; &p < 0.05 vs. O-LEX. n = 7 in each group.
Figure 4
Figure 4
Effects of 12 weeks of aerobic exercise on the GABAergic related protein expressions in the PVN. (A) Immunoreactive bands corresponding to GABAA receptor, gepryrin, GAD67 and GAPDH in the PVN in YC, O-SED, O-LEX and O-HEX group, respectively. (B) Data collections of GABAA receptor, gepryrin and GAD67 protein levels as a ratio to GAPDH. *p < 0.05 vs. YC; **p < 0.01 vs. YC; #p < 0.05 vs. O-SED; &p < 0.05 vs. O-LEX. n = 7 in each group.

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