Early behavioural changes in scrapie-affected mice and the influence of dapsone
Early behavioural changes in scrapie-affected mice and the influence of dapsone
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DOI：
10.1046/j.0953-816x.2001.01645.x
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发表时间：
2001-07-01
影响因子：
3.4
通讯作者：
Rawlins, JNP
中科院分区：
文献类型：
--
作者：
Guenther, K;Deacon, RMJ;Rawlins, JNP
行为测试可以在明显的临床体征出现之前很久揭示羊瘙痒病感染小鼠中的作用（Betmouni等人，1999，Psychobiology，27，63-71）。这些作用可能部分归因于脑中的早期非典型炎症反应（Betmouni等人，1996，Neuroscience，74，1-5）。本研究重复和扩展了这些发现，并检查了长期使用氨苯砜治疗的效果。据报道，这种抗炎化合物在Creutzfeldt-Jakob病的大鼠模型中延迟疾病发作（Manueldinger等人，1998，Lancet，352，456）。尽管本研究中使用的剂量高于Manueldamn等人（1998）的剂量，但在行为学或随后的组织学试验中均未观察到疾病减弱。从第12周左右开始，在羊瘙痒病感染的小鼠中，挖洞（即从饲养笼中的管中取出食物颗粒）减少，可口葡萄糖溶液的消耗也减少。同时，在一个开放的领域增加，饲养在17周左右。自发性交替在这段时间左右受损。在18周左右，倒置屏幕、单杠、旋转杆和静止杆上的运动表现下降。20周时，巢的结构受损。仅在第20周后，当小鼠准备进行组织学检查时，才出现明显的临床体征（活动性降低、弓背姿势、被毛状况不良、膀胱增大）。因此，ME 7羊瘙痒病感染小鼠在疾病过程中表现出神经和行为变化的特征性复杂性，这些变化不能被氨苯砜改善。这些变化早在临床体征突出之前就出现了。
Behavioural testing can reveal effects in scrapie-infected mice long before overt clinical signs appear (Betmouni et al., 1999, Psychobiology, 27, 63-71). These effects may be partly attributable to an early, atypical inflammatory response in the brain (Betmouni et al., 1996, Neuroscience, 74, 1-5). The present study replicated and extended these findings, and examined the effect of chronic treatment with dapsone. This anti-inflammatory compound has been reported to delay disease onset in a rat model of Creutzfeldt-Jakob disease (Manuelidis et al., 1998, Lancet, 352, 456). Although the doses used in the present study were higher than those of Manuelidis et al. (1998), no attenuation of the disease was seen in either behavioural or subsequent histological tests. Burrowing, i.e. displacing food pellets from a tube in the home cage, decreased from around week 12 in scrapie-infected mice, as did consumption of palatable glucose solution. Concurrently, ambulation in an open field increased, as did rearing at around week 17. Spontaneous alternation was impaired around this time. Around 18 weeks, motor performance on an inverted screen, horizontal bar, rotating rod and static rods decreased. Nest construction was impaired at 20 weeks. Overt clinical signs (reduction in mobility, hunched posture, poor coat condition, bladder enlargement) only occurred after week 20, when the mice were prepared for histology. The ME7 scrapie-infected mice thus showed a characteristic complex of neurological and behavioural changes during the course of the disease that were not ameliorated by dapsone. These changes appeared well before clinical signs were prominent.