High fat diet-induced obesity causes a reduction in brain tyrosine hydroxylase levels and non-motor features in rats through metabolic dysfunction, neuroinflammation and oxidative stress

Obesity is a health problem that has been associated with neuroinflammation, decreased cognitive functions and development of neurodegenerative diseases. Parkinson’s disease (PD) is a chronic neurodegenerative condition characterized by motor and non-motor abnormalities, increased brain inflammation, α-synuclein protein aggregation and dopaminergic neuron loss that is associated with decreased levels of tyrosine hydroxylase (TH) in the brain. Diet-induced obesity is a global epidemic and its role as a risk factor for PD is not clear. Herein, we showed that 25 weeks on a high-fat diet (HFD) promotes significant alterations in the nigrostriatal axis of Wistar rats. Obesity induced by HFD exposure caused a reduction in TH levels and increased TH phosphorylation at serine 40 in the ventral tegmental area. These effects were associated with insulin resistance, increased tumor necrosis factor-α levels, oxidative stress, astrogliosis and microglia activation. No difference was detected in the levels of α-synuclein. Obesity also induced impairment of locomotor activity, total mobility and anxiety-related behaviors that were identified in the open-field and light/dark tasks. There were no changes in motor coordination or memory. Together, these data suggest that the reduction of TH levels in the nigrostriatal axis occurs through an α-synuclein-independent pathway and can be attributed to brain inflammation, oxidative/nitrosative stress and metabolic disorders induced by obesity

• Autores: Bittencourt, Aline; Ozorio Brum, Pedro; Tiefensee Ribeiro, Camila; Gasparotto, Juciano; Bortolin, Rafael Calixto; Rodrigues de Vargas, Amanda; Heimfarth, Luana; Farina de Almeida, Roberto; Moreira, José Cláudio Fonseca; de Oliveira, Jade; Pens Gelain, Daniel
• Tipo de recurso: http://purl.org/coar/resource_type/c_816b
• Fecha de publicación: 2020
• Institución: Corporación Universidad de la Costa
• Repositorio: REDICUC - Repositorio CUC
• Idioma: eng
• OAI Identifier: oai:repositorio.cuc.edu.co:11323/7975
• Acceso en línea: https://hdl.handle.net/11323/7975; https://doi.org/10.1080/1028415X.2020.1831261; https://repositorio.cuc.edu.co/
• Palabra clave: Obesity; Parkinson’s disease; Tyrosine hydroxylase; Inflammation; Locomotion; Anxiety; Neuroinflammation; High-fat diet
• Rights: openAccess
• License: CC0 1.0 Universal