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Yue F.,Capital Medical University | Yue F.,Key Laboratory on Neurodegenerative Disease of Ministry of Education | Lu C.,Wincon TheraCells Biotechnologies Co. | Ai Y.,University of Kentucky | And 3 more authors.
Neurobiology of Aging | Year: 2014

Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop β-amyloid (Aβ) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associated changes in Aβ and tau protein in cerebrospinal fluid. The present study was an attempt to specifically address these issues. Cerebrospinal fluid levels of Aβ and phosphorylated tau were measured in 37 and 22 cynomolgus monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from the present study revealed significant age-associated declines in Aβ42 levels but not in Aβ40 and phosphorylated tau levels. This finding appears to parallel changes seen with human aging, in which decreased levels of Aβ42 can be seen in normal older adults, and supporting that cynomolgus monkeys would be a useful model for studying age-related neurologic disorders associated with Alzheimer-like cerebral proteopathy. © 2014 Elsevier Inc.

Yue F.,Capital Medical University | Yue F.,Key Laboratory of Neurodegenerative Diseases | Zeng S.,Guilin Medical College | Wu D.,Capital Medical University | And 5 more authors.
Journal of Neural Transmission | Year: 2012

Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by 99mTc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of 99mTc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys. © 2012 Springer-Verlag.

Wu D.,Capital Medical University | Jiang W.Y.,Peoples Hospital of Sichuan Province | Yang F.,Peoples Hospital of Sichuan Province | Wei S.Y.,Wincon TheraCells Biotechnologies Co. | And 5 more authors.
Journal of Medical Primatology | Year: 2013

Background: Limited physiological data for Tibetan macaques are available at present. This study will provide more rationale for evaluating this species. Methods: Thirty-seven Tibetan macaques (15 males and 22 females) were used in this study. Somatometric measurements, clinical chemistry and hematology parameters, insulin, and C-peptide were analyzed. Results: Females had higher values of waist and waist hip ratio (WHR) than males in somatometric measurements. There were no significant differences between the two genders in hematology. Significant differences between males and females were only found for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in biochemistry testing. In addition, females had higher fasting insulin and C-peptide than males. There was a strongly positive correlation between age and some somatometric parameters. Conclusions: These physiological data will provide veterinarians and researchers with baseline values to evaluate experimental results using Tibetan macaques. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Zou C.,Capital Medical University | Zou C.,Key Laboratory of Neurodegeneration | Zou C.,Guangxi Medical University | Wang S.,Capital Medical University | And 4 more authors.
Cornea | Year: 2012

Purpose: The purpose of this study was to investigate the ultrastructural corneal changes of chronic diabetic monkeys and explore the relationship between advanced glycation end products and ultrastructural changes in diabetic corneas. Methods: A total of 8 cynomolgus monkeys were used in this experiment. Four monkeys were induced into insulin-dependent diabetes mellitus for 4 years. Four age-matched healthy monkeys were used as the controls. Ultrathin sections obtained from the corneas were examined by transmission electron microscopy. Results: Advanced glycation end product immunoreactivity was observed in the epithelial cells, epithelial basement membrane, and stromal keratocytes of diabetic corneas, whereas advanced glycation end product immunoreactivity was not found in the corresponding area in normal corneas. Abnormal collagen fibril bundles of variable thickness were identified in corneal stroma in all diabetic monkeys. Epithelial and endothelial cell degeneration was also observed in 1 diabetic monkey. Conclusions: Abnormal aggregates of collagen fibrils in stromal matrix were common among long-term diabetic monkeys, and the formation of the abnormal collagen fibril aggregates might result from excessive nonenzymatic glycosylation. Copyright © 2012 by Lippincott Williams and Wilkins.

Zhu L.,Beijing Normal University | Zhu L.,University of Pennsylvania | Qiao H.,Beijing Normal University | Qiao H.,University of Pennsylvania | And 13 more authors.
Nuclear Medicine and Biology | Year: 2012

Objectives: Recently, 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine (18F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of 18F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). Methods: To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using 18F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative 18F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding. Results: The radiochemical purity of the 18F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of 18F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction). Conclusions: The pseudo-carrier, AV-149, did not affect the 18F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable 18F-AV-133 to be widely available for routine clinical application in determining changes in monoamine neurons for patient with movement disorders or other psychiatric illnesses. © 2012 Elsevier Inc.

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