Neuroinflammatory, monoaminergic, behavioral and autophagic pathway changes after modulation of beta 2 noradrenergic receptors in an animal model of parkinsonism.

• Grant number: 23/11559-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2024
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Regina Helena da Silva
• Grantee: Regina Helena da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alessandra Mussi Ribeiro

Abstract

Parkinson's Disease (PD) is a chronic, multifactorial, and pathophysiological neurodegenerative disease characterized by the progressive death of dopaminergic neurons, resulting in motor deficits. Some studies show that noradrenergic pathway dysfunction is associated with non-motor symptoms and disease progression. Besides, these studies also suggest that the nigrostriatal pathway dysfunction is secondary to other neural pathway dysfunction in earlier stages of PD. Epidemiological studies indicate that the chronic use of noradrenergic receptor agonists - ²2 (RA²2) is associated with a reduced risk of developing PD. Additionally, experimental studies show that noradrenergic pathway stimulation, through compensatory mechanisms, can increase dopamine release, reduce ±-synuclein expression and microglial activation, produce pro-inflammatory mediators, and modulate autophagic flow. Recently, our research group evaluated the effect of pharmacological modulation of RA²2 agonists in a progressive model of parkinsonism. The main results were reduced motor alterations and ±-synuclein expression in noradrenergic and dopaminergic nuclei. Thus, we hypothesized that chronic stimulation of RA²2 may delay the onset of PD and protect dopaminergic neurons against pathophysiological mechanisms associated with the disease. As the development of effective treatments for PD requires a better understanding of the mechanisms underlying neurodegeneration, we aim to evaluate the pharmacological modulation of RA²2 on neuroinflammatory, monoaminergic, behavioral, and autophagic changes in the animal parkinsonism model. (AU)

Scientific publications

(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 GOIS, AUDERLAN M.; BISPO, JOSE M. M.; SANTOS, EDSON R.; SOUZA, MARINA F.; MELO, JOAO E. C.; MENDONCA, MYLAINE S.; ALMEIDA-SOUZA, THIAGO H.; CAMARGO, ENILTON A.; MEDEIROS, KATTY A. A. L.; LEAL, POLLYANA C.; et al. (3-2 agonist and antagonist adrenoceptors induce neuroprotection in a progressive model of parkinsonism. Neuropharmacology, v. 271, p. 13-pg., 2025-03-05. (23/11559-0)