Mariana Bocca Nejm1, Marcia Jonathas Guimarães-Marques1, Leandro Freitas Oliveira1, Laís Damasceno1, Monica L Andersen2, Sergio Tufik2, Fernando Fonseca3,4, Efrain Olszewer5, Renato Leça6, Antonio Carlo G de Almeida7, Fulvio Alexandre Scorza1, Carla Alessandra Scorza8. 1. Departamento de Neurologia/Neurociência, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), Av. Pedro de Toledo, 699, 1º andar, São Paulo, SP, Brazil. 2. Departamento de Psicobiologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, SP, Brazil. 3. Laboratório de Análises Clínicas da Faculdade de Medicina do ABC, Santo André, SP, Brazil. 4. Departamento de Ciências Farmacêuticas da, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil. 5. Fundação de Apoio à Pesquisa e Estudo na Área de Saúde (FAPES), São Paulo, SP, Brazil. 6. Departamento de Cirurgia II, Faculdade de Medicina do ABC, Santo André, SP, Brazil. 7. Departamento de Engenharia de Biossistemas, Universidade Federal de São João Del Rei (UFSJ), São João Del Rei, MG, Brazil. 8. Departamento de Neurologia/Neurociência, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), Av. Pedro de Toledo, 699, 1º andar, São Paulo, SP, Brazil. carla.scorza@unifesp.br.
Abstract
BACKGROUND: Cardiovascular dysfunctions are common non-motor symptoms in patients with Parkinson's disease (PD) that can result in reduced quality of life and even death. Research in animal models designed to characterize the pathological association between PD and cardiovascular abnormalities is still in its infancy. This study assessed the early impact of the nigrostriatal dopaminergic damage on cardiological features in the unilateral 6-OHDA rat model of PD. METHODS: Male Wistar rats received unilateral intrastriatal injections of 6-OHDA and sham rats were injected with saline. Animals were studied 15 days later. Immunohistochemistry was used for visualization of tyrosine hydroxylase (TH)-positive neurons in the nigrostriatal system. Electrocardiogram recordings of heart rate were performed in conscious rats. Heart levels of vitamin D, inflammatory cytokines and C-reactive protein were assessed through electrochemiluminescence immunoassay, quantitative reverse transcription PCR and turbidimetric method, respectively. RESULTS: We found a post-injury reduction of TH-immunoreactivity of approximately 45% in the substantia nigra pars compacta and 20% in the striatum. Heart rate reduction was found in 6-OHDA-lesioned rats as compared with sham counterparts. Reduced levels of vitamin D and increased levels of inflammatory factors (C-reactive protein, IL-6, TNF-α and TGF-β) were detected in the heart tissue of PD rats in comparison with sham. CONCLUSION: Our findings suggest a link between cardiac tissue changes and cardiac functional changes early after the central dopaminergic damage induced by 6-OHDA. Knowledge of the cardiac abnormalities in the 6-OHDA model is critical in identifying future therapeutic targets and disease-modifying approaches for PD non-motor features.
BACKGROUND:Cardiovascular dysfunctions are common non-motor symptoms in patients with Parkinson's disease (PD) that can result in reduced quality of life and even death. Research in animal models designed to characterize the pathological association between PD and cardiovascular abnormalities is still in its infancy. This study assessed the early impact of the nigrostriatal dopaminergic damage on cardiological features in the unilateral 6-OHDArat model of PD. METHODS: Male Wistar rats received unilateral intrastriatal injections of 6-OHDA and sham rats were injected with saline. Animals were studied 15 days later. Immunohistochemistry was used for visualization of tyrosine hydroxylase (TH)-positive neurons in the nigrostriatal system. Electrocardiogram recordings of heart rate were performed in conscious rats. Heart levels of vitamin D, inflammatory cytokines and C-reactive protein were assessed through electrochemiluminescence immunoassay, quantitative reverse transcription PCR and turbidimetric method, respectively. RESULTS: We found a post-injury reduction of TH-immunoreactivity of approximately 45% in the substantia nigra pars compacta and 20% in the striatum. Heart rate reduction was found in 6-OHDA-lesioned rats as compared with sham counterparts. Reduced levels of vitamin D and increased levels of inflammatory factors (C-reactive protein, IL-6, TNF-α and TGF-β) were detected in the heart tissue of PDrats in comparison with sham. CONCLUSION: Our findings suggest a link between cardiac tissue changes and cardiac functional changes early after the central dopaminergic damage induced by 6-OHDA. Knowledge of the cardiac abnormalities in the 6-OHDA model is critical in identifying future therapeutic targets and disease-modifying approaches for PD non-motor features.
Entities:
Keywords:
Cardiovascular; Heart; Inflammatory mediators; Parkinson disease; Vitamin D
Authors: Valeria C Gonçalves; Daniel J L L Pinheiro; Tomás de la Rosa; Antônio-Carlos G de Almeida; Fúlvio A Scorza; Carla A Scorza Journal: Nutrients Date: 2020-05-26 Impact factor: 5.717