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 AÎ²42-induced neuronal damage, by using primary mouse astrocytes cell cultures and mixed astrocytes-neurons cultures. Furthermore, the possible protective effects of PEA against AÎ²42-induced neuronal toxicity have also been investigated by evaluating neuronal viability, apoptosis, and morphometric parameters. Results: The presence of astrocytes pre-exposed to AÎ²42 (0.5 Î¼M; 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 AÎ²42 pre-exposure induced an increase in the number of neurite aggregations/100 Î¼m 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 Î¼M), applied 1 h before and maintained during AÎ²42 treatment. Conclusion: Astrocytes contribute to AÎ²42-induced neurotoxicity and PEA, by blunting AÎ²42-induced astrocyte activation, improved neuronal survival in mouse astrocyte-neuron co-cultures.
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|Titolo:||Palmitoylethanolamide Blunts Amyloid-Î²ivation and Improves Neuronal Survival in Primary Mouse Cortical Astrocyte-Neuron Co-Cultures|
|Data di pubblicazione:||2018|
|Appare nelle tipologie:||03.1 Articolo su rivista|