Analysis of differential gene expression of dorsal ganglion root cell in a model of diabetes and peripheral diabetic neuropathy

• Grant number: 14/25153-7
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2015 - June 30, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Carlos Amilcar Parada
• Grantee: Carlos Amilcar Parada
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Cesar Renato Sartori

Abstract

Diabetic Peripheral Neuropathy (DPN) manifests in 60% of diabetic patients and counts for one of the major causes of peripheral members amputation. Besides, diabetes is responsible for 30% of all neuropathic pain diagnosed. Even though the electrophysiological and morphological aspects are well described, little is known about its development and progression, impossibilitating effective therapies. It is believed that hyperglycemia and insulin impairment signaling are the main events behind oxidative stress observed in nerves. Several hypothesis try to explain the phenomenon, like enhancement activity of the polliol pathway, greater production of AGES, impairment of neurotrofic support, PKC activity enhancement and mitochondrial failure, but until now there are still many gaps in the disease development knowledge and the cellular populations involved. Besides neurons, there are evidences that glial satellite cell located in the dorsal root ganglia (DRG) actively contribute to inflammation promotion in injury neuropathy, a non-explored fact in DPN. Recent data from our laboratory correlate experimentally DPN development with a shorter period in developing hyperglycemia induced by low doses of streptozotocin (STZ) whether late hyperglycemic rats in the same model did not had DPN. These original data permitted us to establish new model criteria of diabetes induced by STZ more close to the clinic. That said, this project objective is to explore, by DNA microarrays analysis, the major molecules or pathways differentially expressed in neurons and glial satellite cells of DRG from rats model of STZ-induced type I diabetes presenting DPN or not. Further, the possible candidate genes will be validated in the same tissues, by Real-Time PCR and Western Blot. With this approach we expect to find potential genes or pathways that might be enrolled with, allowing future advances in effective treatments or even neuropatic reversion. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE MAGALHAES, SILVIANE F.; MANZO, LUIS P.; DE FARIA, FELIPE M.; DE OLIVEIRA-FUSARO, MARIA C.; NISHIJIMA, CATARINE M.; VIEIRA, WILLIANS F.; BONET, IVAN J. M.; DOS SANTOS, GILSON G.; TAMBELI, CLAUDIA H.; PARADA, CARLOS A.. Inflammatory pain in peripheral tissue depends on the activation of the TNF-alpha type 1 receptor in the primary afferent neuron. European Journal of Neuroscience, v. 53, n. 2, p. 376-389, JAN 2021. (14/25153-7, 17/23485-0)

VIEIRA, WILLIANS F.; DE MAGALHAES, SILVIANE F.; FARIAS, FELIPE H.; DE THOMAZ, ANDRE A.; PARADA, CARLOS A.. Raman spectroscopy of dorsal root ganglia from streptozotocin-induced diabetic neuropathic rats submitted to photobiomodulation therapy. Journal of Biophotonics, v. 12, n. 11, JULY 2019. (15/12673-5, 14/25153-7, 18/05108-8)

PEDRO ATHIE, MARIA CAROLINA; VIEIRA, ANDRE SCHWAMBACH; TEIXEIRA, JULIANA MAIA; DOS SANTOS, GILSON GONCALVES; DIAS, ELAYNE VIEIRA; TAMBELI, CLAUDIA HERRERA; SARTORI, CESAR RENATO; PARADA, CARLOS A.. Transcriptome analysis of dorsal root ganglia's diabetic neuropathy reveals mechanisms involved in pain and regeneration. Life Sciences, v. 205, p. 54-62, JUL 15 2018. (11/23764-0, 14/25153-7)

DO PRADO, FILIPE C.; VIEIRA, WILLIANS F.; DE MAGALHAES, SILVIANE FERNANDES; MAGAYEWSKY BONET, IVAN JOSE; TAMBELI, CLAUDIA H.; PARADA, CARLOS A.. The onset speed of hyperglycemia is important to the development of neuropathic hyperalgesia in streptozotocin-induced diabetic rats. European Journal of Neuroscience, APR 2020. (14/25153-7)

VIEIRA, WILLIANS FERNANDO; MALANGE, KAUE FRANCO; DE MAGALHAES, SILVIANE FERNANDES; PAES LEMES, JULIA BORGES; DOS SANTOS, GILSON GONCALVES; NISHIJIMA, CATARINE MASSUCATO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; DA CRUZ-HOFLING, MARIA ALICE; PARADA, CARLOS AMILCAR; TAMBELI, CLAUDIA HERRERA. Anti-hyperalgesic effects of photobiomodulation therapy (904 nm) on streptozotocin-induced diabetic neuropathy imply MAPK pathway and calcium dynamics modulation. SCIENTIFIC REPORTS, v. 12, n. 1, p. 18-pg., 2022-10-06. (18/05108-8, 15/12673-5, 14/25153-7)

VIEIRA, WILLIANS FERNANDO; MALANGE, KAUE FRANCO; DE MAGALHAES, SILVIANE FERNANDES; DOS SANTOS, GILSON GONCALVES; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; CRUZ-HOFLING, MARIA ALICE; PARADA, CARLOS AMILCAR. Gait analysis correlates mechanical hyperalgesia in a model of streptozotocin-induced diabetic neuropathy: A CatWalk dynamic motor function study. Neuroscience Letters, v. 736, p. 12-pg., 2020-09-25. (15/12673-5, 14/25153-7, 18/05108-8)

DO PRADO, FILIPE C.; VIEIRA, WILLIANS F.; DE MAGALHAES, SILVIANE FERNANDES; MAGAYEWSKY BONET, IVAN JOSE; TAMBELI, CLAUDIA H.; PARADA, CARLOS A.. The onset speed of hyperglycemia is important to the development of neuropathic hyperalgesia in streptozotocin-induced diabetic rats. European Journal of Neuroscience, v. 52, n. 6, p. 10-pg., 2020-04-07. (14/25153-7)