Abstract
BackgroundParkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60. The etiology of the disease is unknown; however, accumulating evidence suggests that mitochondrial defects, oxidative stress, and neuroinflammation play important roles in developing the disease. Current medications for PD can only improve its symptoms, but are unable to halt its progressive nature. Although many therapeutic approaches are available, new drugs are urgently needed for the treatment of PD. Thus, the present study was undertaken to investigate the neuroprotective potential of nerolidol, a sesquiterpene alcohol, on a rotenone-induced experimental model of PD, where male Wistar rats intraperitoneally received rotenone (ROT) at a dose of 2.5 mg/kg of body weight once daily for 4 weeks.ResultsNerolidol, which has antioxidant and anti-inflammatory properties, was injected intraperitoneally at 50 mg/kg of body weight, once daily for 4 weeks, and at 30 min prior to ROT administration. ROT administration significantly reduced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of the antioxidant tripeptide glutathione (GSH). Moreover, ROT increased the levels of the lipid peroxidation product malondialdehyde (MDA), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), and inflammatory mediators (COX-2 and iNOS) in rat brain tissues. Immunostaining of brain tissue sections revealed a significant increase in the number of activated astrocytes (GFAP) and microglia (Iba-1), along with the concomitant loss of dopamine (DA) neurons in the substantia nigra pars compacta and dopaminergic nerve fibers in the striatum of ROT-treated rats. As expected, nerolidol supplementation to ROT-injected rats significantly increased the level of SOD, CAT, and GSH, and decreased the level of MDA. Nerolidol also inhibited the release of proinflammatory cytokines and inflammatory mediators. Finally, nerolidol treatment prevented ROT-induced glial cell activation and the loss of dopaminergic neurons and nerve fibers, and ultimately attenuated ROT-induced dopaminergic neurodegeneration.ConclusionOur findings are the first to show that the neuroprotective effect of nerolidol is mediated through its anti-oxidant and anti-inflammatory activities, which strongly supports its therapeutic potential for the treatment of PD.
Highlights
Parkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60
Parkinson disease is a neurodegenerative disorder that is characterized by a progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and dopaminergic nerve terminal fibers of the striatum that are enriched in the DA transporter [1]
NRD administration prevents the loss of DA neurons in the SNc and DA nerve fibers in the striatum To investigate the beneficial effect of NRD on DA neurodegeneration in ROT-injected rats, tyrosine hydroxylase (TH) immunohistochemical analysis was performed to assess the expression of healthy TH+ DA neurons in the SNc and the tyrosine hydroxylase immunoreactive (TH-ir) DA nerve fibers density in the striatum
Summary
Parkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60. The etiology of the disease is unknown; accumulating evidence suggests that mitochondrial defects, oxidative stress, and neuroinflammation play important roles in developing the disease. The etiology for dopaminergic neuronal degeneration in PD is not completely understood, current evidence suggests that oxidative stress and neuroinflammation play key roles in the pathogenesis of PD [2, 3]. The ROT model recapitulates most of the pathological features observed in human PD pathogenesis, including the loss of DA neurons in SNc, and enhanced oxidative stress and neuroinflammation in the nigrostriatal dopaminergic pathway [2, 6,7,8].
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