The effect of acute and chronic increases in neuromuscular activity on gene expression in small and large dorsal root ganglion neurons: healthy and diabetic rat
| dc.contributor.author | Paddock, Natasha | |
| dc.contributor.examiningcommittee | McCrea, Dave (Physiology and Pathophysiology) Jordan, Larry (Physiology and Pathophysiology) Fernyhough, Paul (Pharmacology and Therapeutics) Gomez-Pinilla, Fernando (Integrative Biology and Physiology) | en_US |
| dc.contributor.supervisor | Gardiner, Phillip (Physiology and Pathophysiology) | en_US |
| dc.date.accessioned | 2016-04-15T20:12:08Z | |
| dc.date.available | 2016-04-15T20:12:08Z | |
| dc.date.issued | 2016 | |
| dc.degree.discipline | Physiology and Pathophysiology | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Dorsal root ganglion (DRG) neurons are responsive to altered neuromuscular activity and play a role in diabetic peripheral neuropathy (DPN). We present evidence that small and large DRG neurons are differentially affected by exercise and diabetes. We examined gene expression in samples of small and large neurons of rat L4/L5 DRG, and the specific responses after exercise and diabetes, to identify potential molecular processes involved in activity-dependent changes. Small and large DRG neurons were collected using laser capture microdissection. Relative mRNA levels were determined using real-time polymerase chain reaction experiments. In study 1, healthy adult rats received treadmill exercise for 1 or 17 weeks, or voluntary wheel exercise for 16 weeks. In study 2, STZ-induced diabetic rats received 15 weeks of sedentary treatment or voluntary wheel exercise. Behavioural testing of thermal latency response was performed on all animals in study 2. In study 1, there were no significant changes in small or large DRG neuron gene expression after acute treadmill exercise. After chronic treadmill exercise, mRNA levels changed relative to healthy sedentary rats in small (↑ 5HT1D; ↓5HT1F) and large (↓ 5HT1A, TrkC, SYN1) DRG neurons. After chronic voluntary wheel exercise, mRNA levels changed relative to healthy sedentary rats in small (↓ 5HT1D, OPRD1, TrkA; ↑ GAP43) and large (↓ 5HT1D, Nav1.6, OPRD1, TrkA, TrkC, SYN1; ↑ 5HT3A, GAP43) DRG neurons. In study 2, there were no significant changes in large DRG neuron gene expression. In small DRG neurons, mRNA levels were changed in the diabetic sedentary group (↓TrkB; ↑5HT1F) as well as the diabetic wheel group (↓ CGRP) relative to healthy sedentary rats. 5HT1A receptor mRNA levels were higher in diabetic sedentary rats relative to diabetic wheel rats. Our results demonstrate that small and large DRG neurons respond, but in different ways, to the duration and intensity of exercise. DRG neurons show a greater response to voluntary compared to forced exercise, and chronic compared to acute exercise. The genetic changes in small DRG neurons of rats with DPN that exercise may be correlated with the positive change in progression of thermal hypoalgesia associated with exercise. | en_US |
| dc.description.note | May 2016 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/31236 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Dorsal root ganglia | en_US |
| dc.subject | Exercise | en_US |
| dc.subject | Gene expression | en_US |
| dc.title | The effect of acute and chronic increases in neuromuscular activity on gene expression in small and large dorsal root ganglion neurons: healthy and diabetic rat | en_US |
| dc.type | doctoral thesis | en_US |