Distribution of the Alpha-Synuclein in the Brain and the Primary Organs of the Rhesus Monkey.

Previous studies have shown that abnormal aggregation of alpha-synuclein (α-syn) protein is a major trigger of neurodegenerative diseases. The expression level of α-syn in different brain regions and the disease-susceptible regions varies with the development of the disease. The expression pattern of the α-syn protein in mouse brain has been precisely described in the literature. Some studies have also reported the ubiquitous expression of the α-syn protein in the central and peripheral in nonhuman primates (NHPs). However, little is known about the expression pattern of α-syn in the brain or in the primary organs of NHPs. Here, we investigated the expression profile of α-syn in different brain regions and the primary organs of NHPs. The α-syn protein was mainly distributed in layers III and V of the cerebral cortex and the hippocampus. In addition, strong immunofluorescent signals were detected in the striatum and the substantia nigra, especially in the globus pallidus and the substantia nigra pars compacta, where the expression was significantly and particularly strong, compared with that in the cerebellum or the cortex. In the cerebellum, intense α-syn signal was observed in the molecular layer, where it was significantly higher than in the nucleus or the medulla. In the brain, the α-syn was always detected both in the cytoplasm and the synapses. Additionally, the α-syn was widely expressed in primary organs. The α-syn signal was higher in the liver and small intestine than in the spleen. Thus, the regions displaying the highest α-syn expression are also those affected during the progression of neurodegenerative diseases. These results may provide basic reference data for the study of multi-systemic mechanism of neurodegenerative diseases.

Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model.

CONTEXT: The uric acid metabolism pathway is more similar in primates and humans than in rodents. However, there are no reports of using primates to establish animal models of hyperuricaemia (HUA). OBJECTIVES: To establish an animal model highly related to HUA in humans. MATERIALS AND METHODS: Inosine (75, 100 and 200 mg/kg) was intraperitoneally administered to adult male rhesus monkeys (n = 5/group). Blood samples were collected over 8 h, and serum uric acid (SUA) level was determined using commercial assay kits. XO and PNP expression in the liver and URAT1, OAT4 and ABCG2 expression in the kidneys were examined by qPCR and Western blotting to assess the effects of inosine on purine and uric acid metabolism. The validity of the acute HUA model was assessed using ulodesine, allopurinol and febuxostat. RESULTS: Inosine (200 mg/kg) effectively increased the SUA level in rhesus monkeys from 51.77 ± 14.48 at 0 h to 178.32 ± 14.47 µmol/L within 30 min and to peak levels (201.41 ± 42.73 µmol/L) at 1 h. PNP mRNA level was increased, whereas XO mRNA and protein levels in the liver were decreased by the inosine group compared with those in the control group. No changes in mRNA and protein levels of the renal uric acid transporter were observed. Ulodesine, allopurinol and febuxostat eliminated the inosine-induced elevation in SUA in tested monkeys. CONCLUSIONS: An acute HUA animal model with high reproducibility was induced; it can be applied to evaluate new anti-HUA drugs in vivo and explore the disease pathogenesis.