Amy Morrison Gyorkos

Short-term exercise increases GDNF protein levels in the spinal cord of young and old rats

Neurotrophic factors may play a role in exercise-induced neuroprotective effects, however it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the current study was to determine if 2 weeks of exercise alters GDNF protein content in the lumbar spinal cord of young and old rats. GDNF protein was quantified via an enzyme-linked immunosorbent assay and Western blot. Immunohistochemical analysis localized GDNF in choline acetyltransferase (ChAT)-positive motor neurons and cell body areas were measured. Involuntary running in the young animals appeared to elicit the greatest increase in GDNF protein content (sixfold increase), followed by swimming (threefold increase) and voluntary running (twofold increase); however there was no significant difference between the modalities of exercise. Low-intensity running of the old animals significantly increased GDNF protein content in the spinal cord. Both young and old exercised animals showed a doubling in ChAT-positive motor neuron cell body areas. These results suggest that GDNF protein content in the spinal cord is modulated by exercise.

Glial cell line-derived neurotrophic factor (GDNF) expression and NMJ plasticity in skeletal muscle following endurance exercise.

Glial cell line-derived neurotrophic factor (GDNF) supports and maintains the neuromuscular system during development and through adulthood by promoting neuroplasticity. The aim of this study was to determine if different modes of exercise can promote changes in GDNF expression and neuromuscular junction (NMJ) morphology in slow- and fast-twitch muscles. Rats were randomly assigned to a run training (run group), swim training (swim group), or sedentary control group. GDNF protein content was determined by enzyme-linked immunosorbant assay. GDNF protein content increased significantly in soleus (SOL) following both training protocols (P<0.05). Although not significant, an increase of 60% in the extensor digitorum longus (EDL) followed swim-training (NS; P<0.06). NMJ morphology was analyzed by measuring α-bungarotoxin labeled post-synaptic end plates. GDNF content and total end plate area were positively correlated. End plate area decreased in EDL of the run group and increased in SOL of the swim group. The results indicate that GDNF expression and NMJ morphological changes are activity dependent and that different changes may be observed by varying the exercise intensity in slow- and fast-twitch fibers.

GDNF content and NMJ morphology are altered in recruited muscles following high-speed and resistance wheel training.

Glial cell line‐derived neurotrophic factor (GDNF) may play a role in delaying the onset of aging and help compress morbidity by preventing motor unit degeneration. Exercise has been shown to alter GDNF expression differently in slow‐ and fast‐twitch myofibers. The aim was to examine the effects of different intensities (10, 20, ~30, and ~40 m·min−1) of wheel running on GDNF expression and neuromuscular junction (NMJ) plasticity in slow‐ and fast‐twitch myofibers. Male Sprague‐Dawley Rats (4 weeks old) were divided into two sedentary control groups (CON4 week, n = 5 and CON6 week, n = 5), two involuntary running groups, one at a low velocity; 10 m/min (INVOL‐low, n = 5), and one at a higher velocity; 20 m/min (INVOL‐high, n = 5), and two voluntary running groups with resistance (VOL‐R, n = 5, 120 g), and without resistance (VOL‐NR, n = 5, 4.5 g). GDNF protein content, determined by enzyme‐linked immunosorbent assay (ELISA), increased significantly in the recruited muscles. Plantaris (PLA) GDNF protein content increased 174% (P < 0.05) and 161% (P < 0.05) and end plate‐stained area increased 123% (P < 0.05) and 72% (P < 0.05) following VOL‐R, and VOL‐NR training, respectively, when compared to age‐matched controls. A relationship exists between GDNF protein content and end plate area (r = 0.880, P < 0.01, n = 15). VOL‐R training also resulted in more dispersed synapses in the PLA muscle when compared to age‐matched controls (P < 0.05). Higher intensity exercise (>30 m/min) can increase GDNF protein content in fast‐twitch myofibers as well as induce changes in the NMJ morphology. These findings help to inform exercise prescription to preserve the integrity of the neuromuscular system through aging and disease.

Exercise-dependent regulation of glial cell line-derived neurotrophic factor (GDNF) expression in skeletal muscle and its importance for the neuromuscular system

The focus of this review is to highlight the importance of glial cell line-derived neurotrophic factor (GDNF) for the motor nervous system. GDNF is the most potent survival factor for motor neurons, where it enhances maintenance and survival of both developing and mature motor neurons in vivo and in vitro. GDNF aids in neuromuscular junction formation, maintenance, and plasticity, where skeletal muscle-derived GDNF may be responsible for this phenomenon. Increased levels of physical activity can increase GDNF protein levels in skeletal muscle, where alterations in acetylcholine and acetylcholine receptor activation may be involved in regulation of these changes observed. With inactivity and disuse, GDNF expression shows different patterns of regulation in the central and peripheral nervous systems. Due to its potent effects for motor neurons, GDNF is being extensively studied in neuromuscular diseases.