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

Figure 1

Parkinson’s disease mechanism of action in the central nervous system and the pharmacokinetic effects of several agents that induce Parkinson-like symptoms. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) crosses the blood-brain barrier to be metabolized in 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase B in the astrocytes. Afterwards, the transportation system of the synaptic cleft assists the intraneuronal MPP+ transfer and transports it further into the mitochondria where it impairs the mitochondrial respiration chain leading to reactive oxygen species production and dopaminergic neuron loss [21]. Similar to MPTP, paraquat could increase reactive oxygen species production, but in contrast to MPTP, it could lead to Lewy body (LB) formation [22]. 6-Hydroxidopamine could also enter the dopaminergic neurons and lead to reactive oxygen species production in the absence of the Lewy body inclusions [23]. Following diffusion to intraneuronal space, rotenone inhibits mitochondrial complex I and promotes the formation of Lewy body inclusions [22, 23]. Abbreviations: 6-OHDA—6-hydroxydopamine; ADP—adenosine diphosphate; ANT—adenine nucleotide translocase; ATP—adenosine triphosphate; BBB—blood-brain barrier; DA—dopamine; LB—Lewy bodies; L-DOPA—levodopa; MAO-B—monoamine oxidase B; MPP+—1-methyl-4-phenylpyridinium; MPTP—1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; OXPHOS—oxidative phosphorylation; ROS—reactive oxygen species; TH—tyrosine; VDAC—voltage-dependent anion channel.