Differential gene expression of dorsal root ganglia cells in a rat model of diabetes and diabetic neuropathy

Author(s)

Maria Carolina Pedro Athié

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2016-06-28

Examining board members

Carlos Amílcar Parada; Gisele Picolo; Daniel Martins de Souza; Helena Cristina Barbosa Sampaio; Joice Maria da Cunha

• Advisor: Carlos Amílcar Parada

Abstract

Peripheral Diabetic Neuropathy (PDN) manifests in 50-60% of types I and II diabetic patients and is the major cause of non-traumatic limb amputation. 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 production observed in the dying nerves. Several hypotheses try to explain the phenomenon, but until now there are still many gaps in the pathogenesis and the plastic changes it generates. Changes in transcriptome and proteome detected by high-throughput techniques, when first symptoms of the disease start to appear, can help understand the molecular events observed in PDN. To achieve this, we proposed a study to analyze, by RNA-Seq and label-free quantitative mass spectrometry, transcriptional and proteomic changes in Dorsal Root Ganglia (DRG) of a rat model for type I diabetes and its respective control. The results presented here show that alterations in genes and proteins expression are already taking place after only two weeks of detection of mechanical sensitivity impairment in hyperglycemic rats¿ hindpaw. Despite the great transcriptome similarity between control and diabetic rats, RNA sequencing comparative analysis already found 66 transcripts differentially expressed between the groups. Proteomic study also revealed alteration in protein expression in hyperglycemic rats DRG¿s: 3 proteins were considered differentially expressed between the two groups. Similarly, function-based categorization pointed to differentially expressed genes and proteins enrolled in oxidative estresse response, inflamation, apoptosis/cell survival, cell proliferation, and hyperalgesia/analgesia. Given their physiological roles, expression alterations in such genes and proteins suggest an alteration in cell metabolic program to switch to a more survival/regenerative one. Our results show that changes in transcriptome and proteomic profile start to appear very early in PDN and that these first alterations might be a strong effort for keeping cell homeostases. 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. Knowing the first cell alterations in PDN might lead to more concrete targets for pharmaceutical interventions, that 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