Improvement of non-motor and motor behavioral alterations associated with Parkinson-like disease in Drosophila melanogaster: Comparative effects of treatments with hesperidin and L-dopa

• Published in: Neurotoxicology (Park Forest South) 2022-03, Vol.89, p.174-183
• Main Authors: Poetini, Márcia Rósula, Musachio, Elize Aparecida Santos, Araujo, Stífani Machado, Bortolotto, Vandreza Cardoso, Meichtry, Luana Barreto, Silva, Neicí Cáceres, Janner, Dieniffer Espinosa, La Rosa Novo, Diogo, Mesko, Marcia Foster, Roehrs, Rafael, Ramborger, Bruna Piaia, Prigol, Marina
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Anxiety; Behavior; Chelation; Complications; Coordination; Disease Models, Animal; Dopamine; Dopamine receptors; Drosophila melanogaster; Flavonoids; Flies; Fruit flies; Grooming; Hesperidin; Hesperidin - pharmacology; Hesperidin - therapeutic use; Insects; Iron; Levodopa; Memory; Motor ability; Movement disorders; Neurodegenerative diseases; Neuroprotection; Parkinson Disease - drug therapy; Parkinson's disease
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2022.02.004

Non-motor alterations such as anxiety and memory deficit may represent early indications of Parkinson’s disease (PD), and therapeutic strategies that reduce non-motor alterations are promising alternatives for the treatment. Therefore, the search for natural compounds that act on motor and non-motor complications is highly relevant. In this sense, we demonstrated the role of hesperidin (Hsd) as a citrus flavonoid and its pharmacological properties as an antioxidant and neuroprotective agent. Our objective was to evaluate Hsd in developing motor and non-motor alterations in a Drosophila melanogaster model of Parkinson-like disease induced by iron (Fe) exposure. The flies were divided into six groups: control, Hsd (10 µM), L-dopa (positive control, 1 mM), Fe (1 mM), Fe + Hsd, and Fe + L-dopa. Motor coordination tests, memory assessment through aversive phototaxy, and anxiety-like behaviors characterized in flies, such as grooming and aggressiveness, were performed. The Hsd attenuated motor and non-motor alterations, such as motor coordination, memory deficits and anxiety-like behaviors, attenuated monoaminergic deficits, and lowered Fe levels in the head of flies. In addition, Hsd prolonged the life of the flies, thereby standing out from the L-dopa-treated group. Thus, Hsd can protect the dopaminergic system from insults caused by Fe, preventing non-motor alterations in PD; Hsd also reduced Fe levels in the flies’ heads, suggesting that iron chelation may represent an important mechanism of action, in addition to its antioxidant action. [Display omitted] •Hsd protected the dopaminergic system from insults caused by Fe.•Hsd prevented the development of motor and non-motor alterations in a Parkinson’s disease model.•Hsd adjusted iron levels in the flies’ head.•Hsd adjusted tyrosine hydroxylase activity, which regulates dopamine and octopamine levels.•Hsd prolonged the lifespan of the flies, performing better than the L-dopa-treated group.