Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Faculty of Earth and Life Sciences, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
Danone Nutricia Research, 3584 CT Utrecht, The Netherlands.
Cells. 2022 Apr 22;11(9):1428. doi: 10.3390/cells11091428.
Astrocytes are specialized glial cells that tile the central nervous system (CNS) and perform numerous essential functions. Astrocytes react to various forms of CNS insults by altering their morphology and molecular profile, through a process known as reactive astrogliosis. Accordingly, astrocyte reactivity is apparent in many neurodegenerative diseases, among which one is Alzheimer's disease (AD). Recent clinical trials on early-stage AD have demonstrated that Fortasyn Connect (FC), a multi-nutrient combination providing specific precursors and cofactors for phospholipid synthesis, helps to maintain neuronal functional connectivity and cognitive performance of patients. Several studies have shown that FC may act through its effects on neuronal survival and synaptogenesis, leading to reduced astrocyte reactivity, but whether FC can directly counteract astrocyte reactivity remains to be elucidated. Hence, we developed an in vitro model of reactive astrogliosis using the pro-inflammatory cytokines TNF-α and IFN-γ together with an automated high-throughput assay (AstroScan) to quantify molecular and morphological changes that accompany reactive astrogliosis. Next, we showed that FC is potent in preventing cytokine-induced reactive astrogliosis, a finding that might be of high relevance to understand the beneficial effects of FC-based interventions in the context of neurodegenerative diseases.
星形胶质细胞是中枢神经系统(CNS)中的特化神经胶质细胞,具有多种重要功能。星形胶质细胞通过改变其形态和分子特征对各种形式的 CNS 损伤做出反应,这一过程被称为反应性星形胶质细胞增生。因此,在许多神经退行性疾病中都能观察到星形胶质细胞的反应性,其中之一是阿尔茨海默病(AD)。最近针对早期 AD 的临床试验表明,Fortasyn Connect(FC)是一种提供特定磷脂合成前体和辅助因子的多营养组合,可以帮助维持患者的神经元功能连接和认知表现。多项研究表明,FC 可能通过影响神经元存活和突触发生来发挥作用,从而减少星形胶质细胞的反应性,但 FC 是否可以直接对抗星形胶质细胞的反应性仍有待阐明。因此,我们使用促炎细胞因子 TNF-α 和 IFN-γ 以及自动化高通量测定法(AstroScan)开发了体外反应性星形胶质细胞增生模型,以定量伴随反应性星形胶质细胞增生的分子和形态变化。接下来,我们表明 FC 能够有效预防细胞因子诱导的反应性星形胶质细胞增生,这一发现可能对于理解基于 FC 的干预措施在神经退行性疾病背景下的有益作用具有重要意义。