The effect of AdipoRon on learning and memory, oxidative stress indices, BDNF and PSD95 in the hippocampus of 6-hydroxy dopamine-induced Parkinson model in adult male rats

Abstract

Parkinson's disease (PD) is associated with the destruction of dopaminergic neurons in the pars compacta of the substantia nigra and the decrease of dopamine in the striatum. With the progress of this disease, the effectiveness of existing drugs decreases. While motor symptoms are the most recognized manifestation of PD, patients may also suffer from non-motor symptoms such as cognitive impairment. As an adiponectin receptor agonist, AdipoRon has shown neuroprotective effects in different models of neurodegenerative diseases. Based on this, in this study, the effect of AdipoRon on learning and memory, oxidative stress and the expression of BDNF and PSD95 proteins in the hippocampus of adult male parkinsonian rats induced by 6-hydroxydopamine injection were investigated. Methods: Sixty adult male rats were randomly divided into 6 groups: 1) Sham group: animals were sham surgry and then received DMSO intranasally (IN) for 21 days. 2) Parkinson's disease (PD) group: After inducing the PD model with 6-hydroxydopamine, they received DMSO intranasally (IN) for 21 days. 3) Parkinson's group + levodopa (Levodopa + PD) received levodopa at a dose of 10 mg/kg for 21 days. 4) Parkinson's group + AdipoRon 0.1 (PD+Adipo 0.1), 5) Parkinson's group + AdipoRon 1 (PD+Adipo 1), and 6) Parkinson's group + AdipoRon 10 (PD+Adipo 10). In groups 4 to 6, AdipoRon was adminstered intranasally at doses of 0.1, 1 and 10 µg/rat for 21 days. After finishing the treatment period, Barnes Maze test and novel object recognition test were performed. One day later, the animals were anesthetized by ketamine and xylazine, and the hippocampal tissue of the animals was removed to examine the oxidative stress status as well as the protein expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density 95 (PSD-95). Results: Induction of PD caused impairment in cognitive functions, increased oxidative stress and decreased expression of BDNF and PSD95 proteins in the hippocampus. However, intranasal administration of AdipoRon at doses of 1 µg and 10 µg improved cognitive function. In addition, unilateral injection of 6-OHDA led to increased levels of reactive oxygen species (ROD) and decreased total antioxidant capacity (TAC) and antioxidant enzymes (SOD, GPx), and expression of BDNF and PSD95 proteins in hippocampal tissue. However, AdipoRon at a dose of 10 μg significantly reduced these biochemical changes in the hippocampus of PD animals.