MPTP Induces Systemic Parkinsonism in Middle-Aged Cynomolgus Monkeys: Clinical Evolution and Outcomes

Abstract

In this study, we developed a systemic PD model in middle-aged cynomolgus monkeys using individualized low-dose MPTP, to explore effective indicators for the early prediction of clinical outcomes. MPTP was not stopped until the animals showed typical PD motor symptoms on days 10 to 13 after MPTP administration when the Kurlan score reached 10; this abrogated the differences in individual susceptibility to MPTP. The clinical symptoms persisted, peaking on days 3 to 12 after MPTP withdrawal (rapid progress stage), and then the Kurlan score plateaued. A Kurlan score at the end of the rapid progress stage [15 reflected stable or slowly-progressive PD, while a score\15 indicated spontaneous recovery. The entire clinical evolution and outcome of the systemic PD model was characterized in this study, thus providing options for therapeutic and translational research.

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…Upon the onset of PD, they assessed the behavioral tests using the video recording, clinical rating, and measurement of overall home-cage activity levels and observed that the PD progression was at peak during the 3rd–12th day, and then the Kurlan score plateaued (>15). Subsequently to the rapid PD progression, a Kurlan score > 15 and at the end of the 3rd month showed a weakened risk of spontaneous rescue [ 145 ]. They observed stable PD symptoms for three months and suggested the model as an effective PD model for investigating the Parkinsonian [ 145 ].…”

“…Subsequently to the rapid PD progression, a Kurlan score > 15 and at the end of the 3rd month showed a weakened risk of spontaneous rescue [ 145 ]. They observed stable PD symptoms for three months and suggested the model as an effective PD model for investigating the Parkinsonian [ 145 ]. Seo et al (2019) administered 0.2 mg MPTP/kg intramuscularly in female Macaca fascicularis and observed MPTP toxicity through the decrease of global activity, dopamine transporter activity, and increased PD impairment scores from the 4th–48th week after the first MPTP injection.…”

Salidroside Protects against MPP+‐Induced Neuronal Injury through DJ‐1‐Nrf2 Antioxidant Pathway

“…MPTP- (1-methyl-4-phenyl-1,2,5,6- tetrahydropyridine-) induced neuronal injury in neuron cells and neurodegenerative disorder in animals are usually used for the study of the pathogenesis and treatment of PD [16–18]. The neurotoxin MPTP causes neurotoxicity through the active metabolite MPP+ (1-methyl-4-phenylpyridinium).…”

LRRK2-G2019S Synergizes With Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation That Precede Nigrostriatal Degeneration

“…[67][68][69][72][73][74][75] Middle age is recognized as a critical temporal window, whereby mDAns progressively become more vulnerable, and the microenvironmental SNpc milieu slowly shifts towards an "harmful" phenotype characterized by increased glial reactivity, oxidative stress, and the gradual loss of dopamine-mediated mitigation of inflammation . 22,46,102,103,119 Based on our previously published findings and literature reports, coupled with pilot studies, we herein selected a very low, sub-threshold dose of 0.1 mg Kg -1 , which induces a mild inflammatory response in young adult (3 M-old) as opposed to the exaggerated inflammatory response of aged (≥ 20 M-old) mice. 66,68,76 This dose did not induce sickness behavior (assessed by changes in body weight, food and fluid intake, and locomotor activity) when compared to NaCl injected mice.…”