N-acetylcysteine decreases dopamine transporter availability in the non-lesioned striatum of the 6-OHDA hemiparkinsonian rat

Virel, Ana; Johansson, Jarkko; Axelsson, Jan; Ericsson, Madelene; Laterveer, Rutger; Ögren, Mattias; Orädd, Greger; Mo, Susanna Jakobson; Bjerkén, Sara af

doi:10.1016/j.neulet.2021.136420

Cited by 2 publications

(1 citation statement)

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“…Still, as previously assumed, some researchers have supported the protective influence of NAC against induced parkinsonism [ 38 , 101 , 102 , 103 ], revealing that, several days after a severe oxidative insult, NAC can provide long-term neuroprotection of striatal TH fibers [ 100 , 104 , 105 ]. Moreover, research from Virel and colleagues also indicated that at an early time point, NAC does not protect striatal dopaminergic fibers against 6-OHDA insult [ 106 ], which pinpoints that regeneration of the lesioned striatum may be achieved at later stages, as reported for other antioxidants [ 107 ]. Hence, we believe that multiple time points and different treatment pipelines are necessary to really address NAC’s temporal and therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

N-Acetylcysteine Treatment May Compensate Motor Impairments through Dopaminergic Transmission Modulation in a Striatal 6-Hydroxydopamine Parkinson’s Disease Rat Model

et al. 2023

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Preventing degeneration and the loss of dopaminergic neurons (DAn) in the brain while mitigating motor symptoms remains a challenge in Parkinson’s Disease (PD) treatment development. In light of this, developing or repositioning potential disease-modifying approaches is imperative to achieve meaningful translational gains in PD research. Under this concept, N-acetylcysteine (NAC) has revealed promising perspectives in preserving the dopaminergic system capability and modulating PD mechanisms. Although NAC has been shown to act as an antioxidant and (neuro)protector of the brain, it has yet to be acknowledged how this repurposed drug can improve motor symptomatology and provide disease-modifying properties in PD. Therefore, in the present work, we assessed the impact of NAC on motor and histological deficits in a striatal 6-hydroxydopamine (6-OHDA) rat model of PD. The results revealed that NAC enhanced DAn viability, as we found that it could restore dopamine transporter (DAT) levels compared to the untreated 6-OHDA group. Such findings were positively correlated with a significant amelioration in the motor outcomes of the 6-OHDA-treated animals, demonstrating that NAC may, somehow, be a modulator of PD degenerative mechanisms. Overall, we postulated a proof-of-concept milestone concerning the therapeutic application of NAC. Nevertheless, it is extremely important to understand the complexity of this drug and how its therapeutical properties interact with the cellular and molecular PD mechanisms.

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