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Advanced Neurology Alzheimer’s and Parkinson’s disease rodent models

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Figure 2. Parkinson’s disease (PD) rodent models used in the past 5 years. (A) Type of PD model (induced, genetic, both, or combined in the same
animal) used by the 1,222 selected studies for the review over the last 5 years. (B) Type and quantity of PD models (induced, genetic, both, or combined
in the same animal) used by the 1,222 selected studies for the review in each of the 5 assessed years (2019 – 2023). (C) Type of the 1,255 PD models
reported (induced, genetic, or combined in the same animal) by the selected studies over the last 5 years. (D) Type and quantity of the 1,255 PD models
reported (induced, genetic, or combined in the same animal) by the selected studies in each of the 5 assessed years (2019 – 2023). (E) Detailed PD model
used over the last 5 years (from high to low percentages: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); α-synuclein (genetic and induced);
6-hydroxydopamine (6-OHDA); rotenone; Parkin/PINK knockout; others; reserpine; LRRK2 knockout; lipopolysaccharide (LPS); paraquat; combined
model; and haloperidol). (F) Detailed PD model used in each of the 5 assessed years (2019 – 2023) (from higher to lower numbers: MPTP; 6-OHDA;
α-synuclein overexpression; rotenone; α-synuclein pre-formed fibrils (PFF); Parkin/PINK knockout; others; reserpine; LRRK2 knockout; LPS; paraquat;
combined model; and haloperidol).

non-dopaminergic cells such as glial cells and serotonergic resulting in cellular damage and eventual cell death.
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neurons. This metabolic cascade yields an intermediate Furthermore, administration of MPTP results in the
metabolite (MPDP+) and subsequently MPP+. MPP+ cytosolic accumulation of α-Syn within dopaminergic
(the active toxin) is released into the extracellular space neurons, adding another hallmark of human disease.
and selectively accumulates within dopaminergic neurons However, it is noteworthy that classical Lewy bodies,
through the dopamine transporter (DAT), owing to its characteristic of PD, have not been observed in the brains
high DAT affinity. Inside the mitochondria, MPP+ exerts of MPTP-intoxicated patients or non-human primates.
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its deleterious effects by inhibiting complex I, thereby For decades, the MPTP-induced mouse model of PD has
disrupting the electron transfer from complex I to been extensively used to mimic the features of sporadic
ubiquinone (Q) and impairing oxidative phosphorylation. PD, despite its inability to fully replicate all PD symptoms.
This disruption not only diminishes ATP synthesis but In addition, the rapid onset of neuronal death induced
also triggers the activation of transitional pores and by MPTP means that this model fails to capture the
subsequent release of cytochrome C. Consequently, these progressive neurodegeneration observed in PD patients,
is an escalation in reactive oxygen species (ROS) levels, resembling instead a late-stage PD. 19

Volume 3 Issue 3 (2024) 4 doi: 10.36922/an.2903