PLC-PKC signaling pathway is significantly enhanced by endurance training and participates in neuroplasticity after spinal cord injury
Katarína Bimbová 1 Mária Bačová 1 Alexandra Kisucká 1 Nadežda Lukáčová 1
Growth factors (GF) are proteins that regulate several aspects of cellular function, including differentiation, proliferation and migration during the development of nervous system and promoting regeneration after traumatic injuries. It is well known that the binding of growth factors to the specific receptors stimulates signalling pathways which affects survival, neuroplasticity and regeneration in the central nervous system.
The aim of our study was to determine the effect of endurance training on the expression of growth factors and stimulation of intracellular signaling pathways. Wistar rats were divided into 4 groups: 1) control group; 2) trained-group (treadmill training- 5 days/week for 6 weeks with increasing intensity (27 cm/s - 46.6 cm/s); 3) Th9 compression-group (SCI + 6weeks survival); 4) six-weeks training + SCI (6 weeks survival) group (T+SCI). The effect of endurance training was studied at Th8-Th10 level. Spinal cord tissue was used for: RT-PCR (to detect the expression of growth factors and their receptors- BDNF/TrkB, GDNF/GFRα); Western blot (to determine the protein level of BDNF/TrkB, and signaling molecules PLC, CAMK, PKC involved in two major GF-stimulated PLC-PKC; PLC-CAMK pathways), and immunohistochemical labeling (to observe which cells express GF).
Our results showed, that 6-weeks endurance training significantly (p<0.001) increased the mRNA-expression and the GF-protein levels compared to control. Increased GF expression was identified mainly in astrocytes. Our in-depth analysis demonstrates, that spontaneous neuroplasticity seen in SCI-group is GF specific and is activated through both PLC-PKC and PLC-CAMK signaling pathways. In T+SCI group, long-term exercise effectively influenced growth factors immunoreactivity in astrocytes, glycine- and GABAergic neurons. In addition, long-term physical activity markedly increased the activity of PLC-PKC signaling responsible for neuroplasticity at lesion site after SCI. Our results provide a quantitative insight into how GF induced by endurance training activate signaling pathways responsible for neuroplasticity, and how control functional outcome of experimental animals after T+SCI.