Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease

“…The inconsistency in findings can be attributed to varying degrees of nigrostriatal dopaminergic denervation. Furthermore, dopamine neurons of old rats are more vulnerable to 6-OHDA than those of young rats ( Barata-Antunes et al, 2020 ). Accordingly, elderly lesioned animals could have more severe dopamine neuron loss than young-lesioned rats before the behavioral analyses, which could explain the increasingly severe dyskinetic movements ( Bez et al, 2016 ; Lanza et al, 2019 ), although the striatal dopamine contents at the end of the experiment by Lanza et al (2019) were not so different between young- and old-lesioned model rats.…”

Rat Models of Vocal Deficits in Parkinson’s Disease

“…Oxidopamine, or 6-hydroxydopamine (6-OHDA), is a catecholaminergic neurotoxin classically used to model PD by inducing significant neurodegeneration of the nigrostriatal dopamine system by unilateral or bilateral infusion to the medical forebrain bundle or the striatum [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. The well-established 6-OHDA rat model has been used to study behavioral changes, mechanisms of cell death, and therapies that could potentially improve PD signs [ 48 , 54 , 55 , 56 , 57 , 58 ].…”

Sudden death in a rat model of Parkinson's disease

“…The use of rodents of variable age has been shown to impact data quality in many areas of scientific research (17). However, in PD research, most studies did not use aged animals (18). Specifically, regarding the 6-OHDA-induced rat model of PD, it has been established that the best strategy would be to perform lesional surgery when animals are young and develop the disease phenotype with aging, which might result in a decreased animal death rate (18).…”

“…However, in PD research, most studies did not use aged animals (18). Specifically, regarding the 6-OHDA-induced rat model of PD, it has been established that the best strategy would be to perform lesional surgery when animals are young and develop the disease phenotype with aging, which might result in a decreased animal death rate (18). Considering the age-related criteria for designing experiments with the 6-OHDA model, the case of sudden death described in this study is in accordance with the proposals established in the literature.…”