Voluntary Exercise Increases Gdnf Protein Content and Endplate Area in Hindlimb Muscle of Male and Female Rats

Abstract

Increased expression of target-derived neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), may help protect against the age-related decline in neuromuscular function. The purpose of this study was to compare GDNF protein content in male and female rat skeletal muscle and investigate morphological changes of the neuromuscular junction (NMJ) with age and voluntary exercise. Male and female Sprague-Dawley rats were exercised in voluntary running wheels for 2 weeks, 4 weeks, or 6 months. Plantaris (PLA) and soleus (SOL) were removed and processed for GDNF protein content in skeletal muscle by an enzyme-linked immunosorbent assay. Tissues were bound with α-bungarotoxin to analyze the structure of the NMJ. GDNF protein levels were higher in hindlimb skeletal muscles from sedentary females as compared to muscle from age-matched males. In SOL muscle of 6-week-old sedentary females the GDNF protein concentration (pg/g tissue weight) was 45.75±8.16, which was significantly higher than age-matched males at 1.55±0.02. For both sexes, exercised animals had higher GDNF protein concentrations in PLA and SOL than their age-matched sedentary counterparts. Exercised 12-week-old males had the highest overall GDNF protein concentration of 98.20±1.36. Endplate area increased with sedentary aging for both sexes. There was no difference in endplate dispersion with sedentary aging in male rats. However, in female rats, endplate dispersion increased with sedentary aging. The results indicate that there are sex differences in levels of GDNF expression. Because GDNF concentration is higher in female rats, this may explain why females are more protected against diseases with a neurological component.

Note:
Funding Declaration: None

Conflicts of Interest: None

Ethical Approval: All animal experiments were performed in accordance with the “Guide for the Care and Use of Laboratory Animals” (National Research Council) and protocols were approved by the Institutional Animal Care and Use Committee at Western Michigan University.

Keywords: neuromuscular junction, endplate morphology