Apoptosis in CA1 and CA3.

Background
Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures.
Methods
Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used.
Results
A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 μm; HGINV 37 ± 5 μm; WB 28 ± 3 μm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils.
Conclusion
The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.

### 背景
贾第虫病（Giardiasis）与锌缺乏症已被认定为全球范围内的严重健康问题。尽管已知贾第虫感染会引发锌耗竭，但目前尚无研究探讨该感染是否会导致脑结构发生改变。
### 方法
本研究使用三组沙鼠：对照组（第1组），以及分别于出生后第3天经口接种两株肠道贾第虫（Giardia intestinalis）滋养体的HGINV组与WB组（第2、3组）。实验选取五个时间节点进行检测，涵盖感染建立、贾第虫种群增殖、寄生虫自然清除以及感染后阶段。实验采用QuantiChrome锌检测试剂盒、克紫（cresyl violet）染色法以及TUNEL技术。
### 结果
感染后可见组织锌含量显著降低（p<0.01），且该现象持续存在。HGINV组与WB组中75%的沙鼠均出现细胞构筑改变：海马角（cornus ammonis，CA1-CA3）区域可见异位锥体细胞；在沙鼠60日龄与90日龄时，CA1区的分层结构缺失清晰可见。齿状回（dentate gyrus, DG）自30日龄起即可观察到背侧层变薄与腹侧层异常增厚。在小脑中，14日龄时外颗粒层（external granular layer, EGL）厚度显著增加（p<0.01），该变化持续至21日龄（对照组：3±0.3 μm；HGINV组：37±5 μm；WB组：28±3 μm）；浦肯野细胞计数显示其数量显著减少，且分子层中散在大量凋亡胞体；在60日龄与90日龄的沙鼠中，可见颗粒细胞异位症与浦肯野细胞异位现象。感染沙鼠小脑与海马的细胞凋亡模式存在差异。
### 结论
本研究发现的形态学改变提示，出生后早期贾第虫感染引发的锌耗竭会影响神经元迁移；本研究首次证实了贾第虫感染-锌耗竭与脑结构损伤之间的关联。该损伤或可解释贾第虫感染相关的精神运动/认知迟缓现象。本研究结果令人警醒：已知锌代谢与信号通路异常参与包括自闭症在内的多种脑部疾病的发生发展。