Related Experiment Video
Updated: Aug 19, 2026
Genetic Study of Axon Regeneration with Cultured Adult Dorsal Root Ganglion Neurons
Published on: August 17, 2012
Early gene responses of trophic factors in nerve regeneration differ in experimental type 1 and type 2 diabetic
Christopher R Pierson1, Weixian Zhang, Yuichi Murakawa
1Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Abstract:
We have previously suggested that alterations in sequential early gene responses of trophic factors (IGF-1 -->c-fos-->NGF) contribute to impaired peripheral nerve regeneration in type 1 diabetic BB/W-rats. To study the role these responses may play in type 2 diabetic nerve regeneration, BB/Z-rats were subjected to sciatic nerve crush injury. The expression of IGF-1, c-fos, NGF and the receptors p75 and IGF-1R were determined at the protein and mRNA levels in sciatic nerve distal to the crush site by immunoblotting and semi-quantitative RT-PCR. In situ hybridization was performed to assess the cellular localization of IGF-1, NGF, p75, and IGF-1R mRNA and immunohistochemistry served to localize the source of p75 and IGF-1R protein expression. The data were compared to those of type 1 diabetic BB/Wor-rats and non-diabetic controls. Increased expression of IGF-1 in Schwann cells is the first growth factor response to injury and peaked at 0.5 hours (h) in control, 2 h in type 2 rats, and 24 h in type 1 rats. IGF-1R was expressed in Schwann cells and its expression was asynchronous to IGF-1 expression in type 1 rats but remained synchronous with IGF-1 in control and type 2 animals. The expression of the immediate early proto-oncogene c-fos exhibited an initial peak at 6 h in control animals, 24 h in type 2, and 2 days (d) in type 1 animals. The initial peak of NGF expression occurred at 6 h in non-diabetic rats, 24 h in type 2, and 2 d in type 1 diabetic rats. The expression of p75 was delayed and attenuated in type 1 diabetic rats; however, in type 2 diabetic rats it was similar to that of non-diabetic rats. These data indicate that early gene responses following nerve damage are significantly less perturbed in type 2 compared to type 1 diabetes. These differences may account for the more efficient nerve regeneration seen in type 2 diabetic polyneuropathy.
Insights
Peripheral nerve regeneration is less impaired in type 2 diabetes due to less perturbed early gene responses, unlike in type 1 diabetes. This suggests differences in growth factor signaling pathways influence nerve repair outcomes.
Area of Science:
- Neuroscience
- Diabetology
- Molecular Biology
Background:
- Peripheral nerve regeneration is crucial for recovery from nerve injury.
- Type 1 diabetes is associated with impaired nerve regeneration, potentially due to altered early gene responses.
- Understanding these responses in type 2 diabetes is vital for explaining differing regeneration outcomes.
Purpose of the Study:
- To investigate the role of early gene responses (IGF-1, c-fos, NGF) in peripheral nerve regeneration in type 2 diabetic rats.
- To compare these responses in type 2 diabetic rats with type 1 diabetic and non-diabetic controls.
- To elucidate the cellular localization and temporal expression of key growth factors and their receptors.
Main Methods:
- Sciatic nerve crush injury model in BB/Z (type 2 diabetic), BB/W (type 1 diabetic), and control rats.
- Analysis of protein and mRNA expression of IGF-1, c-fos, NGF, p75, and IGF-1R using immunoblotting and RT-PCR.
- In situ hybridization and immunohistochemistry to determine cellular localization of gene and protein expression.
Main Results:
- Early gene responses, including IGF-1, c-fos, and NGF expression, were significantly delayed in type 1 diabetic rats compared to controls.
- Type 2 diabetic rats showed less perturbation in the timing and expression levels of these early genes compared to type 1 diabetic rats.
- IGF-1 receptor (IGF-1R) expression remained synchronous with IGF-1 in control and type 2 diabetic rats, but asynchronous in type 1 diabetic rats.
Conclusions:
- Early gene responses following nerve injury are less disrupted in type 2 diabetes than in type 1 diabetes.
- The more efficient nerve regeneration observed in type 2 diabetic polyneuropathy may be attributed to these less perturbed molecular responses.
- These findings highlight critical differences in the molecular mechanisms underlying nerve regeneration in different diabetic models.
