摘要
代谢型谷氨酸受体5(mGluR5)在整个前脑和海马体中高度表达。多条证据支持这一受体在大脑发育和发育障碍中所起的作用,以及在诸如阿尔茨海默病(AD)的神经退行性疾病中起到的作用。在本研究中,采用免疫细胞化学方法研究了mGluR5在唐氏综合症(DS)患者的海马体发育过程和患有DS和AD的成年人中的表达模式。mGluR5在人类海马体发育的孕早期阶段(9孕周)表达,在心室/脑室下区具有强劲表达。我们在唐氏综合症海马体内观察发现了一个持续的具有相似时间和空间的神经元表达模式。然而,在唐氏综合症中我们发现其持续增加产前mGluR5在白质星形胶质细胞的表达。此外,我们观测到了成人的DS患者联合广泛AD相关的神经变性(DS-AD)增加了mGluR5在周围的淀粉样蛋白斑块的星形胶质细胞中的表达。体外实验数据进一步确认了在人类星形胶质细胞中的淀粉样蛋白-β和mGluR5之间存在调节串扰。这些发现证明在人类海马体中mGluR5的发育调控作用,并提出这个受体在早期发育中的唐氏综合症海马体中的星状胶质细胞中发挥作用,以及对相关联的AD病症发病的潜在贡献。
关键词: 阿尔茨海默病,星形胶质细胞,发展,唐氏综合征,海马体,代谢型谷氨酸受体5
Current Alzheimer Research
Title:Metabotropic Glutamate Receptor 5 in Down's Syndrome Hippocampus During Development: Increased Expression in Astrocytes
Volume: 11 Issue: 7
Author(s): A. M. Iyer, J. van Scheppingen, I. Milenkovic, J. J. Anink, D. Lim, A. A. Genazzani, H. Adle-Biassette, G. G. Kovacs and E. Aronica
Affiliation:
关键词: 阿尔茨海默病,星形胶质细胞,发展,唐氏综合征,海马体,代谢型谷氨酸受体5
摘要: Metabotropic glutamate receptor 5 (mGluR5) is highly expressed throughout the forebrain and hippocampus. Several lines of evidence support the role of this receptor in brain development and developmental disorders, as well as in neurodegenerative disorders like Alzheimer’s disease (AD). In the present study, the expression pattern of mGluR5 was investigated by immunocytochemistry in the developing hippocampus from patients with Down's syndrome (DS) and in adults with DS and AD. mGluR5 was expressed in developing human hippocampus from the earliest stages tested (9 gestational weeks), with strong expression in the ventricular/subventricular zones. We observed a consistent similar temporal and spatial neuronal pattern of expression in DS hippocampus. However, in DS we detected increased prenatal mGluR5 expression in white matter astrocytes, which persisted postnatally. In addition, in adult DS patients with widespread ADassociated neurodegeneration (DS-AD) increased mGluR5 expression was detected in astrocytes around amyloid plaque. In vitro data confirm the existence of a modulatory crosstalk between amyloid-β and mGluR5 in human astrocytes. These findings demonstrate a developmental regulation of mGluR5 in human hippocampus and suggest a role for this receptor in astrocytes during early development in DS hippocampus, as well as a potential contribution to the pathogenesis of ADassociated pathology.
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Cite this article as:
Iyer M. A., van Scheppingen J., Milenkovic I., Anink J. J., Lim D., Genazzani A. A., Adle-Biassette H., Kovacs G. G. and Aronica E., Metabotropic Glutamate Receptor 5 in Down's Syndrome Hippocampus During Development: Increased Expression in Astrocytes, Current Alzheimer Research 2014; 11 (7) . https://dx.doi.org/10.2174/1567205011666140812115423
DOI https://dx.doi.org/10.2174/1567205011666140812115423 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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