Establishment of aspinocerebellar ataxias model in cynomolgus monkeys

Abstract

：Objective To explore themethod for establishing an animal model of spinocerebellar ataxias (SCAs) in cynomolgusmonkeys. Methods Two adult male cynomolgus monkeys were subjected to intraperitoneal,intravenous and stereotactic injections of 3- acetylpyridine (3-AP) at the interval of 6months. During stereotactic injection, 3-AP was administered to damage the centralcerebellar nuclei (fastigial nucleus, dentate nucleus, and emboliform nucleus). Abehavioral evaluation system (including clinical behavioral assessment, feedingexperiments and horizontal rotary experiment) was established to assess the coordinatedmovement of the eynomolgus monkeys after the injections. Results Intraperitoneal injectionof 3-AP at 8 folds of the effective dose failed to elicit ataxia in the monkeys, andintravenous 3-AP injection 6 months later at 6 folds of the effective dose also failed tocause ataxia. Stereotactic injection of 3-AP for damaging the central cerebellar nucleiresulted in obvious ataxia (P<0.05), which maintained for 2 months and was relieved 3months after the injection. Conclusion Stereotactic injection of 3-AP to damage thecentral nuclei, other than intraperitoneal or intravenous injections, can successfullyproduce acute SCAs model in cynomolgus monkeys. Behavioral evaluations including clinicalbehavioral assessment, feeding experiments and horizontal rotary experiment are feasibleto validate the establishment of the SCAs model. Key words: Spinocerebellar Ataxia; StereotacticInjection; 3-acetylpyridine; Animal model