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Advanced Neurology Alzheimer’s and Parkinson’s disease rodent models
Figure 1. PRISMA flow diagram for systematic review conducted on Parkinson’s disease animal studies from 2019 to 2023
induced models, 261 (20.8%) genetic models, and 13 (1%) 3.1. Induced models
combined models.
3.1.1. MPTP
Figures 2E and F contain detailed information about the
PD models utilized. The top three rodent PD models over the Among the most commonly used PD models are
past 5 years were, respectively, 1-methyl-4-phenyl-1,2,3,6- those induced by neurotoxins, with MPTP standing
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tetrahydropyridine (MPTP) (44.3%), α-Syn (genetic and as a prominent example. In 1982, several intriguing
pre-formed fibrils [PFF]) (21.1%), and 6-hydroxydopamine medical cases emerged, involving young patients
(6-OHDA) models (17.7%). Upon segregating the α-Syn who exhibited sudden-onset symptoms. Initially,
group into genetic and induced models, MPTP remained psychiatrists misattributed these symptoms to catatonic
the most used model (n = 556 [44.3%]), followed by the schizophrenia due to their classic manifestations
6-OHDA model (n = 222 [17.7%]), α-Syn genetic model resembling PD symptoms. Subsequent investigation
(n = 222 [15.9%]), rotenone model (n = 75 [6%]), and revealed a common denominator among these patients:
PFF α-Syn model (n = 65 [5.2%]). Eight percent of studies the use of a new “synthetic heroin” containing MPTP, a
used alternative models such as Parkin/PINK knockouts, neurotoxic contaminant found in the “street preparation”
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reserpine injections, LRRK2 knockouts, lipopolysaccharide of 1-methyl-4-phenyl-4-propionoxypiperidine. This
(LPS) injections, paraquat injections, and haloperidol analog of the narcotic meperidine induces irreversible
injections. One percent of studies used combined models, and severe Parkinsonian syndrome in both humans
in which animals were subjected to multiple models (e.g., and monkeys, although with a favorable and almost
LRRK2 knockout mice receiving PFF α-Syn injection; A53T immediate response to levodopa (L-dopa) treatment.
α-Syn transgenic mice receiving PFF α-Syn injection; mice MPTP, characterized by its high lipophilicity, can
receiving MPTP and PFF α-Syn injections). In addition, transverse the blood–brain barrier, therefore presenting
1.7% of studies used other models, including the proteus an economical and straightforward option for inducing
mirabilis-induced model, vesicular monoamine transporter PD through peripherical administration. Once within
(VMAT2) deficiency mice, proteasome inhibitor lactacystin- the brain, MPTP undergoes enzymatic conversion by
induced model, and DJ-1 knockout mice, among others. monoamine oxidase (MAO) type B, an enzyme found in
Volume 3 Issue 3 (2024) 3 doi: 10.36922/an.2903

