Palmitoylethanolamide Blunts Amyloid-β42-Induced Astrocyte Activation and Improves Neuronal Survival in Primary Mouse Cortical Astrocyte-Neuron Co-Cultures
Palmitoylethanolamide Blunts Amyloid-β42-Induced Astrocyte Activation and Improves Neuronal Survival in Primary Mouse Cortical Astrocyte-Neuron Co-Cultures
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DOI：
10.3233/jad-170699
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Tomasini, Maria Cristina
中科院分区：
文献类型：
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作者：
Beggiato, Sarah;Borelli, Andrea Celeste;Tomasini, Maria Cristina
背景资料：基于星形胶质细胞在脑内稳态中的关键作用以及神经元和星形胶质细胞之间存在的强代谢合作，已经表明星形胶质细胞功能障碍可能导致和/或促成神经炎症和神经变性过程。旨在神经保护和神经炎症减少的治疗方法可能证明在减缓这些疾病的进展方面特别有效。内源性脂质介质棕榈酰乙醇胺（PEA）显示神经保护和抗（神经）炎症特性，并表现出有趣的潜力作为一种新的治疗阿尔茨海默病的diseases.Objective和方法：我们首先评估是否星形胶质细胞可以参与调节A β 42诱导的神经元损伤，通过使用原代小鼠星形胶质细胞细胞培养和混合星形胶质细胞神经元培养。此外，PEA对A β 42诱导的神经元毒性的可能的保护作用也进行了研究，通过评估神经元的活力，细胞凋亡，和形态参数。结果：存在的星形胶质细胞预暴露于A β 42（0.5 μ M; 24小时）诱导的神经元活力减少在原代小鼠星形胶质细胞神经元共培养。此外，在这些实验条件下，观察到神经元凋亡核的数量增加和MAP-2阳性神经元的数量减少。最后，与对照相比，星形胶质细胞A β 42预暴露诱导了每100 μ m神经突聚集体数量的增加（即，未处理的）星形胶质细胞-神经元共培养物。这些影响没有观察到在培养的神经元中存在的星形胶质细胞预暴露于PEA（0.1 μ M），应用1小时前，并保持在A β 42 treatment.Conclusion：星形胶质细胞有助于A β 42诱导的神经毒性和PEA，通过钝化A β 42诱导的星形胶质细胞激活，提高小鼠星形胶质细胞神经元共培养的神经元存活。
Background: Based on the pivotal role of astrocytes in brain homeostasis and the strong metabolic cooperation existing between neurons and astrocytes, it has been suggested that astrocytic dysfunctions might cause and/or contribute to neuroinflammation and neurodegenerative processes. Therapeutic approaches aimed at both neuroprotection and neuroinflammation reduction may prove particularly effective in slowing the progression of these diseases. The endogenous lipid mediator palmitoylethanolamide (PEA) displayed neuroprotective and anti(neuro) inflammatory properties, and demonstrated interesting potential as a novel treatment for Alzheimer's disease.Objective and Methods: We firstly evaluated whether astrocytes could participate in regulating the A beta 42-induced neuronal damage, by using primary mouse astrocytes cell cultures and mixed astrocytes-neurons cultures. Furthermore, the possible protective effects of PEA against A beta 42-induced neuronal toxicity have also been investigated by evaluating neuronal viability, apoptosis, and morphometric parameters.Results: The presence of astrocytes pre-exposed to A beta 42 (0.5 mu M; 24 h) induced a reduction of neuronal viability in primary mouse astrocytes-neurons co-cultures. Furthermore, under these experimental conditions, an increase in the number of neuronal apoptotic nuclei and a decrease in the number of MAP-2 positive neurons were observed. Finally, astrocytic A beta 42 pre-exposure induced an increase in the number of neurite aggregations/100 mu m as compared to control (i.e., untreated) astrocytes-neurons co-cultures. These effects were not observed in neurons cultured in the presence of astrocytes pre-exposed to PEA (0.1 mu M), applied 1 h before and maintained during A beta 42 treatment.Conclusion: Astrocytes contribute to A beta 42-induced neurotoxicity and PEA, by blunting A beta 42-induced astrocyte activation, improved neuronal survival in mouse astrocyte-neuron co-cultures.