Parkinson’s Disease-Induced Zebrafish Models: Focussing on Oxidative Stress Implications and Sleep Processes

Abstract

The complex yet not fully understood pathophysiology of Parkinson’s disease includes an important molecular component consisting of oxidative status changes, thus leading to oxidative stress occurrence. While no particular evidence has been reported that describes the relationship between oxidative stress and the molecular mechanisms behind Parkinson’s disease development, animal model studies has shown that oxidative stress induction could modulate Parkinson’s disease symptomatology. Despite the inability to perfectly replicate human disease in animals and despite that Parkinson’s disease has not been reported in any animal species, animal modeling is one of the most important tools in understanding the complex mechanisms of human disorders. In this way, this study is aimed at detailing this particular relationship and describing the molecular mechanisms underlying Parkinson’s disease in animal models, focusing on the potential advantages and disadvantages of zebrafish in this context. The information relevant to this topic was gathered using major scientific database research (PubMed, Google Scholar, Web of Science, and Scopus) based on related keywords and inclusion criteria. Thus, it was observed that oxidative stress possesses an important role in Parkinson’s disease as shown by numerous animal model studies, many of which are based on rodent experimental models. However, an emerging impact of the zebrafish model was observed in the research of Parkinson’s disease pathological mechanisms with regard to disease development factors and the cause-effect relationship between oxidative stress and comorbidities (such as depression, hyposmia, fatigue, sleep disturbances, and cognitive deficits) and also with regard to the pharmacological potential of antioxidant molecules in Parkinson’s disease treatment.

The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

“…Besides, the behaviors and phenotypes demonstrated by zebrafish are relatable to human behaviors. For example, neurotoxin-induced zebrafish exhibits movement impairments such as decreased swimming speed and abnormal swimming behavior, which is equally translated to bradykinesia-like symptoms in PD patients ( Hughes et al, 2020 ; Robea et al, 2020 ). In terms of genetic factors, genome sequencing analysis revealed that the zebrafish genome is 70% similar to the human genome ( Howe et al, 2013 ; Shehwana and Konu, 2019 ), with 80% of the genes located at the same chromosome and in the same order, implying conserved synteny between these two species ( Barbazuk et al, 2000 ; Howe et al, 2013 ).…”

“…The discovery of MPTP has opened a new promising opportunity in PD studies because this compound can easily cross the blood brain barrier (BBB) ( Zeng et al, 2018 ). MPTP is metabolized in glial cells by monoamine oxidase B (MAO-B), which causes the conversion of MPTP to its active metabolite, MPP + ( Bajpai et al, 2013 ; Robea et al, 2020 ). Due to its similar structure with dopamine, MPP + is then transported into DA neurons by dopamine transporter protein (DAT) ( Fernagut, 2016 ).…”

“…Inside the neurons, MPP + is concentrated inside the mitochondria where it blocks mitochondrial electron transport chain through binding with mitochondrial complex I ( Zawada et al, 2011 ). The binding of MPP + with complex I perturb the subsequent electron transport chain, leading to insufficient energy generation (in the form of ATP) and increased ROS production ( Perier and Vila, 2012 ; Robea et al, 2020 ).…”

“…Recent investigation suggested that the γ1-synuclein is functionally similar to human α-synuclein ( Barnhill et al, 2020 ). The knockdown of SNCB and SNCG1 genes in zebrafish caused a significant reduction in motor activity and lowered the level of dopamine in the brain ( Milanese et al, 2012 ), indicating that zebrafish β- and γ1-synuclein proteins are required for movement regulation and dopamine homeostasis ( Toni and Cioni, 2015 ; Vaz et al, 2018 ; Robea et al, 2020 ).…”

Loss of parla Function Results in Inactivity, Olfactory Impairment, and Dopamine Neuron Loss in Zebrafish

“…The neuronal circuitries involved in movement in zebrafish are well characterized, with essential molecular mechanisms being highly conserved and analogous to humans. Moreover, despite the remarkable anatomical differences between fish and mammals, it has been shown that more than 70% of all human disease genes have functional homologs in zebrafish [ 17 ]. Zebrafish models of PD have and continue to contribute to our better understanding of familial PD.…”