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亨廷顿病转基因 BACHD 大鼠模型嗅上皮和犁鼻器上皮细胞的差异细胞平衡。

Differential Cellular Balance of Olfactory and Vomeronasal Epithelia in a Transgenic BACHD Rat Model of Huntington's Disease.

机构信息

Department of Anatomy, Rostock University Medical Centre, 18057 Rostock, Germany.

Rudolf-Zenker-Institute for Experimental Surgery, Rostock University Medical Centre, 18057 Rostock, Germany.

出版信息

Int J Mol Sci. 2022 Jul 10;23(14):7625. doi: 10.3390/ijms23147625.

DOI:10.3390/ijms23147625
PMID:35886975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9316117/
Abstract

For neurodegenerative diseases such as Huntington's disease (HD), early diagnosis is essential to treat patients and delay symptoms. Impaired olfaction, as observed as an early symptom in Parkinson´s disease, may also constitute a key symptom in HD. However, there are few reports on olfactory deficits in HD. Therefore, we aimed to investigate, in a transgenic rat model of HD: (1) whether general olfactory impairment exists and (2) whether there are disease-specific dynamics of olfactory dysfunction when the vomeronasal (VNE) and main olfactory epithelium (MOE) are compared. We used male rats of transgenic line 22 (TG22) of the bacterial artificial chromosome Huntington disease model (BACHD), aged 3 days or 6 months. Cell proliferation, apoptosis and macrophage activity were examined with immunohistochemistry in the VNE and MOE. No differences were observed in cellular parameters in the VNE between the groups. However, the MOE of the 6-month-old HD animals showed a significantly increased number of mature olfactory receptor neurons. Other cellular parameters were not affected. The results obtained in the TG22 line suggest a relative stability in the VNE, whereas the MOE seems at least temporarily affected.

摘要

对于亨廷顿病(HD)等神经退行性疾病,早期诊断对于治疗患者和延缓症状至关重要。嗅觉障碍是帕金森病的早期症状之一,也可能是 HD 的一个关键症状。然而,HD 嗅觉缺陷的报道很少。因此,我们旨在研究 HD 的转基因大鼠模型中:(1)是否存在一般嗅觉障碍,以及(2)比较犁鼻器(VNE)和主嗅觉上皮(MOE)时是否存在疾病特异性嗅觉功能障碍的动态变化。我们使用雄性转基因系 22 号(TG22)的细菌人工染色体亨廷顿病模型(BACHD)大鼠,年龄分别为 3 天和 6 个月。用免疫组织化学法检测 VNE 和 MOE 中的细胞增殖、凋亡和巨噬细胞活性。VNE 中两组间细胞参数无差异。然而,6 个月大的 HD 动物的 MOE 显示成熟嗅觉受体神经元数量显著增加。其他细胞参数不受影响。TG22 系的结果表明 VNE 相对稳定,而 MOE 似乎至少暂时受到影响。

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本文引用的文献

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Validation of behavioral phenotypes in the BACHD rat model.BACHD 大鼠模型中行为表型的验证。
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Early deficits in olfaction are associated with structural and molecular alterations in the olfactory system of a Huntington disease mouse model.早期嗅觉功能障碍与亨廷顿病小鼠模型嗅球系统的结构和分子改变有关。
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Motivational Impairment is Accompanied by Corticoaccumbal Dysfunction in the BACHD-Tg5 Rat Model of Huntington's Disease.
动机障碍伴随着亨廷顿病 BACHD-Tg5 大鼠模型的皮质伏隔核功能障碍。
Cereb Cortex. 2019 Dec 17;29(11):4763-4774. doi: 10.1093/cercor/bhz009.
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Olfactory bulb atrophy and caspase activation observed in the BACHD rat models of Huntington disease.亨廷顿病 BACHD 大鼠模型中观察到嗅球萎缩和半胱天冬酶激活。
Neurobiol Dis. 2019 May;125:219-231. doi: 10.1016/j.nbd.2019.02.002. Epub 2019 Feb 6.
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Main Olfactory and Vomeronasal Epithelium Are Differently Affected in Niemann-Pick Disease Type C1.主要嗅觉和犁鼻器上皮在尼曼-皮克病 C1 型中受到不同影响。
Int J Mol Sci. 2018 Nov 12;19(11):3563. doi: 10.3390/ijms19113563.
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Sexual behavior and testis morphology in the BACHD rat model.BACHD 大鼠模型中的性行为和睾丸形态。
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The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function.亨廷顿病的BACHD大鼠模型在运动功能测试组中表现出特定缺陷。
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