Transcriptome analysis of dorsal root ganglia's diabetic neuropathy reveals mechanisms involved in pain and regeneration

Author(s)

Pedro Athie, Maria Carolina ^[1] ; Vieira, Andre Schwambach ^[1] ; Teixeira, Juliana Maia ^[1] ; dos Santos, Gilson Goncalves ^[1] ; Dias, Elayne Vieira ^[1] ; Tambeli, Claudia Herrera ^[1] ; Sartori, Cesar Renato ^[1] ; Parada, Carlos A. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Biol Inst, Struct & Funct Biol Dept, POB 6109, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 205, p. 54-62, JUL 15 2018.
• Web of Science Citations: 4

Abstract

Peripheral diabetic neuropathy (DN) manifests in nearly 60% of diabetic patients, being pain its most debilitating symptom. Although electrophysiological and morphological aspects are well described, little is known about its development and progression, undermining effective therapies. Hyperglycemia and insulin signaling impairment are considered the triggering events of oxidative stress observed in the dying nerves, however there are still many gaps in the knowledge of intracellular plastic changes it generates. Aims: In this study we aimed to evaluate the early transcriptome changes in DN when the first symptoms of the disease start to appear. Main methods: Next-Generation Sequencing of messenger RNA (RNA-Seq) of L4 and L5 dorsal root ganglia (DRG) four weeks post-diabetes induction in a rat model for type 1 diabetes. Key findings: RNA sequencing found 66 transcripts differentially expressed between diabetic and control groups, related mainly to the following biological processes: inflammation, hyperalgesia/analgesia, cell growth and cell survival. Given their roles, the differentially expressed genes suggest an attempt to switch to a survival/regenerative program. Significance: Our results show that changes in the transcriptome profile start to appear early in the course of DN and might be related to secure cell homeostasis. Hence, the present data may indicate how DRG cells are responding to hyperglycemia in its early stages and which mechanisms first fail to respond, further leading to cell damage and cell death. Early screening of cell alterations in DN might lead to more concrete targets for pharmaceutical interventions, which could more efficiently delay cell damage. (AU)

• FAPESP's process: 11/23764-0 - Analysis of differential gene expression of dorsal ganglion root cell in a model of Diabetes and Peripheral Diabetic Neuropathy
• Grantee: Maria Carolina Pedro Athié
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/25153-7 - Analysis of differential gene expression of dorsal ganglion root cell in a model of diabetes and peripheral diabetic neuropathy
• Grantee: Carlos Amilcar Parada
• Support Opportunities: Regular Research Grants