Study of photobiomodulation effects on the mitochondrial metabolism of dorsal root ganglia primary afferent neurons in a model of Peripheral Diabetic Neuropathy

• Grant number: 19/21158-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): July 01, 2020
• Effective date (End): June 30, 2024
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Marucia Chacur
• Grantee: Willians Fernando Vieira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 21/10982-1 - Influence of transcranial near infrared radiation in cerebral blood flow through blood-oxygenation-level dependent (BOLD) signal in patients with major depressive disorder (MDD), BE.EP.PD

Abstract

About 425 million people around the world are Diabetic, and approximately 60 % develop Peripheral Diabetic Neuropathy (PDN), which is characterized by moderate to severe pain involving the upper and lower limbs. The painful symptoms appear after metabolic alterations in the Dorsal Root Ganglia (DRG) afferent neurons and in the Schwann cells from the peripheral nerves, causing it progressive degeneration. These metabolic alterations are characterized by a reduced oxygen consumption and adenosine triphosphate (ATP) production, Mitochondrial Membrane Potential (MMP) reduction and accumulation of Reactive Oxygen Species (ROS), due to deleterious effects of the hyperglycemia over the mitochondrial metabolism. The metabolic overload and the oxidative stress caused by the hyperglycemia lead to an unbalanced gene and protein expression, disturbing signaling pathways linked to the mitochondrial activity, including the peroxiredoxin 5 (PRDX5), glutaredoxin 5 (GLRX5), HIF-1A, FoxO (PI3-K, Akt, mTOR), PKCµ, PKA, and AMPK. Despite efforts to make an early diagnosis and stop the progression of the PDN, there is no globally-available effective treatment, due to lack of full understanding of the disease pathophysiology. In this context, the photobiomodulation therapy (PBMT) seems to be an interesting therapeutic resource, once its action mechanism is highly associated to the mitochondrial complexes activation. PBMT comprises endogenous chromophore-mediated athermic processes, involving photophysical and photochemical events at various biological scales. These processes result in therapeutic effects, including analgesia. Based on that, the aim of this project is to investigate the PBMT (904 nm) anti-hyperalgesic effect on PDN, focused on the mitochondrial metabolism of the DRG afferent neurons. (AU)