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帕金森病患者血清对培养中的大鼠中脑多巴胺能神经元具有补体依赖性毒性。

Parkinsonian serum carries complement-dependent toxicity for rat mesencephalic dopaminergic neurons in culture.

作者信息

Defazio G, Dal Toso R, Benvegnù D, Minozzi M C, Cananzi A R, Leon A

机构信息

FIDIA Research Laboratories, Abano Terme, Italy.

出版信息

Brain Res. 1994 Jan 7;633(1-2):206-12. doi: 10.1016/0006-8993(94)91541-5.

Abstract

The presence of antibodies recognizing specific epitopes of dopaminergic neurons in serum of patients suffering of Parkinson's Disease (PD) as well as their capability to induce neuronal damage was investigated utilizing serum-free dissociated mesencephalic-striatal co-cultures. High affinity dopamine (DA) and GABA uptakes were assessed as specific, functional markers of dopaminergic and GABAergic cell viability, respectively. Heat-inactivated serum samples from 18 and 13 patients suffering from idiopathic and vascular parkinsonism, respectively and from 18 neurologic controls, were added to co-cultures on day 4 in vitro. Twenty four hours later, reconstituted rabbit complement was added for 60 min and uptake parameters as well as immunocytochemical staining for tyrosine hydroxylase (TH)-containing cells were subsequently assessed. DA, but not GABA, uptake was significantly decreased only when complement was added to cultures containing serum samples from 14 out of 18 patients with idiopathic parkinsonism and 3 out of 13 patients with vascular parkinsonism (Fisher test, P < 0.01). Complement addition to cultures containing serum samples from seropositive parkinsonian patients significantly reduced immunocytochemical staining of TH-containing cells. Seropositive and seronegative patients did not differ in demographic and clinical features. These results suggest that a complement-dependent humoral immune response occurs mainly in idiopathic parkinsonian patients, but its clinical relevance remains to be established.

摘要

利用无血清解离中脑-纹状体共培养物,研究了帕金森病(PD)患者血清中识别多巴胺能神经元特异性表位的抗体的存在情况及其诱导神经元损伤的能力。分别将高亲和力多巴胺(DA)和GABA摄取评估为多巴胺能和GABA能细胞活力的特异性功能标志物。分别来自18例特发性帕金森病患者、13例血管性帕金森病患者以及18例神经学对照的热灭活血清样本,在体外培养第4天添加到共培养物中。24小时后,加入重组兔补体60分钟,随后评估摄取参数以及对含酪氨酸羟化酶(TH)细胞的免疫细胞化学染色。仅当补体添加到含有18例特发性帕金森病患者中14例以及13例血管性帕金森病患者中3例血清样本的培养物中时,DA摄取而非GABA摄取显著降低(Fisher检验,P < 0.01)。向含有血清反应阳性帕金森病患者血清样本的培养物中添加补体,显著降低了含TH细胞的免疫细胞化学染色。血清反应阳性和血清反应阴性患者在人口统计学和临床特征方面无差异。这些结果表明,补体依赖性体液免疫反应主要发生在特发性帕金森病患者中,但其临床相关性仍有待确定。

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