The Effects of Aging and Exercise on Glial Cell Line‐Derived Neurotrophic Factor Content in Rat Hearts
Authors: Alves Gabriel Almeida , Spitsbergen John 
Published: June 2021

Heart function is regulated by the sensory nervous system and the two branches of the autonomic nervous system, the sympathetic and parasympathetic nervous systems. Neural development, plasticity, and survival of these branches of the nervous system are controlled by neurotrophic factors such as the glial cell line‐derived neurotrophic factor (GDNF). Studies in our laboratory have shown that aging can shift the innervation pattern in mesenteric vessels from a balanced sensory/sympathetic pattern to a predominately sympathetic pattern and this is associated with an increase in blood pressure. However, the same studies suggest that exercise is associated with an increase in GDNF protein content in mesenteric vessels, a restored balance of innervation, and a lowering of blood pressure. Little is known about how aging and exercise impacts neurotrophic factor expression in cardiac muscle. Therefore, the purpose of this study was to measure GDNF protein content in the heart of rats at different ages and to investigate the effects of exercise on GDNF protein levels. Control groups consisted of 4‐week‐old, 14‐week‐old, 6‐month‐old, 12‐month‐old, and 18‐month‐old sedentary rats (5 or 6 animals per group). In the exercise study, 4‐week‐old, 6‐month‐old, and 12‐month‐old rats were placed in cages with access to voluntary running wheels and were allowed to exercise for 10 weeks (4‐week‐old), or 6 months (6‐ and 12‐month‐old). Sedentary and exercised animals were euthanized and cardiac tissues were removed. Each heart was divided into three parts: right atria (RA), left atria (LA), and ventricles (VT). Tissues were processed and neurotrophic factor protein content was measured using enzyme‐linked immunosorbent assay. GDNF protein content in right atria (0.95 ± 0.14pg of GDNF/mg of tissue), left atria (0.91 ± 0.29pg of GDNF/mg of tissue), and ventricles (0.54 ± 0.35pg of GDNF/mg of tissue) of 4‐week‐old animals was significantly higher than that in heart chambers of older animals (6‐month‐old sedentary RA: 0.17 ± 0.02pg, LA: 0.14 ± 0.07pg, VT: 0.03 ± 0.02pg of GDNF/mg of tissue; 12–month‐old sedentary RA: 0.02 ± 0.01pg, LA: 0.018 ± 0.012pg of GDNF/mg of tissue, VT: Non‐detectable; 18‐month‐old sedentary RA: 0.000172 ± 0.000170pg, LA: 0.00128 ± 0.00236pg of GDNF/mg of tissue, VT: Non‐detectable). The results show that exercise significantly increased GDNF protein content in all heart chambers, in all age‐matched groups (14‐week‐old sedentary: RA: 1.20 ± 0.17pg, LA: 1.30 ± 0.14pg, VT: 1.27 ± 0.10pg of GDNF/mg of tissue and 14‐week‐old exercised: RA: 2.97 ± 0.27pg, LA: 2.06 ± 0.23pg, VT: 2.57 ± 0.32pg of GDNF/mg of tissue; 12‐month‐old exercised RA: 0.25 ± 0.07pg, LA: 0.11 ± 0.03pg, VT: 0.02 ± 0.01pg of GDNF/mg of tissue; 18‐month‐old exercised RA: 0.18 ± 0.21pg, LA: 0.04 ± 0.03pg, VT: 0.006 ± 0.006pg of GDNF/mg of tissue). These results suggest that GDNF protein content decreases with aging in all heart chambers and that exercise increases GDNF protein content in all heart chambers. The observed lowering of GDNF content with age may contribute to altered neural function observed in aged individuals, while the increased GDNF expression observed following exercise could help explain beneficial effects of exercise on cardiac innervation.Support or Funding InformationNIH 1 R15 AG022908‐01A2/NSF 0552517This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.