Quantification of Non-Motor Symptoms in Parkinsonian Cynomolgus Monkeys.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that features motor and non-motor deficits. The use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine neuron degeneration has been widely practiced to produce reliable animal models of PD. However, most previous preclinical studies focused on motor dysfunction, and few non-motor symptoms were evaluated. Thus far, there is a lack of comprehensive investigations of the non-motor symptoms in animal models. OBJECTIVES: In this study, we aim to use a battery of behavioral methods to evaluate non-motor symptoms in MPTP-induced non-human primate PD models. METHODS: Cognitive function, sleep, and psychiatric behaviors were evaluated in MPTP-treated cynomolgus monkeys. The tests consisted of a delayed matching-to-sample (DMTS) task, the use of a physical activity monitor (PAM), an apathy feeding task (AFT), the human intruder test (HIT), novel fruit test (NFT), and predator confrontation test (PCT). In addition, we tested whether the dopamine receptor agonist pramipexole (PPX) can improve these non-motor symptoms. RESULTS: The present results show that the MPTP-treated monkeys exhibited cognitive deficits, abnormal sleep, and anxiety-like behaviors when compared to the control monkeys. These symptoms were relieved partially by PPX. CONCLUSIONS: These results suggest that MPTP-induced PD monkeys displayed non-motor symptoms that were similar to those found in PD patients. PPX treatment showed moderate therapeutic effects on these non-motor symptoms. This battery of behavioral tests may provide a valuable model for future preclinical research.

[VcDsbA enhances bioflim formation by stimulating MSHA expression in Vibrio cholera].

Objective: Biofilm plays an important role during the infection cycle of Vibrio cholerae. In this study, we try to demonstrate the role of VcDsbA in the biofilm formation of V. cholerae. Methods: By making the VcDsbA inframe knock-out construct, the vcdsbA null mutant (ΔdsbA) strain was obtained. And the complemented strain (CΔdsbA) was constructed by transferring a plasmid-coded VcDsbA expressed under the control of arabinose to ΔdsbA strain. Crystal violet staining assay was used to analyze the biofilm formation in the wild-type (WT), ΔdsbA and CΔdsbA strains. V. cholerae strains containing msh promoter luxCDABE transcriptional fusion were used to analyze the transcriptional level. Results: The ΔdsbA and CΔdsbA strains were constructed successfully. Biofilm formation analysis shows that the ability of biofilm formation of ΔdsbA was significantly reduced compared with WT, whereas CΔdsbA could form even stronger biofilm than WT does. Luminescence expression by Pmsh shows that VcDsbA enhanced msh expression. VcDsbA enhances the biofilm formation of V. cholerae by involving in the regulation of msh expression level. VcDsbA up-regulates msh expression probably through helping the folding of a msh expression activator. Conclusion: VcDsbA plays an important role in the biofilm formation of V. chlerae, which makes the bacteria better survive in their living niche.