食蟹猴脊髓小脑性共济失调模型的制作研究

目的 探讨食蟹猴脊髓小脑性共济失调(SCAs)模型的制作. 方法选取2只成年雄性食蟹猴,在不同的时间段内分别采用腹腔注射3-乙酰吡啶(3-AP)、静脉注射3-AP及立体定向注射3-AP损毁小脑中央核群(顶核、齿状核、栓状核)的方法制作食蟹猴SCAs模型,并建立行为学评价体系(行为学评定、取食实验、水平旋转实验等)用于食蟹猴共济运动的评估. 结果首先采用腹腔注射3-AP 8倍有效剂量并观察12周,行为学评价体系结果未出现有关共济失调的症状;再次采用静脉注射3-AP6倍的有效剂量并观察12周,行为学评价体系结果未出现有关共济失调的症状;最后立体定向注射3-AP损毁小脑中央核群,行为学评价体系结果统计分析显示造模后8周内均较造模前差异有统计学意义(P<0.05),而造模后12周起又逐步恢复至造模前状态. 结论立体定向注射3-AP损毁小脑中央核群方法可以制作食蟹猴SCAs的急性模型,行为学评定、取食实验、水平旋转实验适用于该模型的评价.

Establishment of a spinocerebellar ataxias model in cynomolgus monkeys

Objective To explore the method for establishing an animal model of spinocerebellar ataxias (SCAs) in cynomolgus monkeys. Methods Two adult male cynomolgus monkeys were subjected to intraperitoneal, intravenous and stereotactic injections of 3- acetylpyridine (3-AP) at the interval of 6 months. During stereotactic injection, 3-AP was administered to damage the central cerebellar nuclei (fastigial nucleus, dentate nucleus, and emboliform nucleus). A behavioral evaluation system (including clinical behavioral assessment, feeding experiments and horizontal rotary experiment) was established to assess the coordinated movement of the eynomolgus monkeys after the injections. Results Intraperitoneal injection of 3-AP at 8 folds of the effective dose failed to elicit ataxia in the monkeys, and intravenous 3-AP injection 6 months later at 6 folds of the effective dose also failed to cause ataxia. Stereotactic injection of 3-AP for damaging the central cerebellar nuclei resulted in obvious ataxia (P<0.05), which maintained for 2 months and was relieved 3 months after the injection. Conclusion Stereotactic injection of 3-AP to damage the central nuclei, other than intraperitoneal or intravenous injections, can successfully produce acute SCAs model in cynomolgus monkeys. Behavioral evaluations including clinical behavioral assessment, feeding experiments and horizontal rotary experiment are feasible to validate the establishment of the SCAs model.