The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson's Disease.

Abstract

A pharmacological and genetic blockade of the dopamine D3 receptor (D3R) has shown to be neuroprotective in models of Parkinson's disease (PD). The anxiolytic drug buspirone, a serotonin receptor 1A agonist, also functions as a potent D3R antagonist. To test if buspirone elicited neuroprotective activities, C57BL/6 mice were subjected to rotenone treatment (10mg/kg i.p for 21 days) to induce PD-like pathology and were co-treated with increasing dosages of buspirone (1, 3, or 10 mg/kg i.p.) to determine if the drug could prevent rotenone-induced damage to the central nervous system (CNS). We found that high dosages of buspirone prevented the behavioural deficits caused by rotenone in the open field test. Molecular and histological analyses confirmed that 10 mg/kg of buspirone prevented the degeneration of TH-positive neurons. Buspirone attenuated the induction of interleukin-1β and interleukin-6 expression by rotenone, and this was paralleled by the upregulation of arginase-1, brain-derived neurotrophic factor (BDNF), and activity-dependent neuroprotective protein (ADNP) in the midbrain, striatum, prefrontal cortex, amygdala, and hippocampus. Buspirone treatment also improved mitochondrial function and antioxidant activities. Lastly, the drug prevented the disruptions in the expression of two neuroprotective peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). These results pinpoint the neuroprotective efficacy of buspirone against rotenone toxicity, suggesting its potential use as a therapeutic agent in neurodegenerative and neuroinflammatory diseases, such as PD.

• Authors: Sarah Thomas Broome, Alessandro Castorina
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 3 (Feb 06 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35163768 (Publication Type: Journal Article)

Chemical References

• Adcyap1 protein, mouse
• IL1B protein, mouse
• Interleukin-1beta
• Interleukin-6
• Neuroprotective Agents
• Pituitary Adenylate Cyclase-Activating Polypeptide
• interleukin-6, mouse
• Rotenone
• Vasoactive Intestinal Peptide
• Buspirone

Topics

• Animals
• Buspirone (administration & dosage, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Injections, Intraperitoneal
• Interleukin-1beta (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Neuroprotective Agents (administration & dosage, pharmacology)
• Parkinson Disease (drug therapy, etiology, genetics, psychology)
• Pituitary Adenylate Cyclase-Activating Polypeptide (genetics, metabolism)
• Rotenone (toxicity)
• Vasoactive Intestinal Peptide (genetics, metabolism)