Aβ Chronic Exposure Promotes an Activation State of Microglia through Endocannabinoid Signalling Imbalance.

Autor: Scipioni, Lucia, Tortolani, Daniel, Ciaramellano, Francesca, Fanti, Federico, Gazzi, Thais, Sergi, Manuel, Nazaré, Marc, Oddi, Sergio, Maccarrone, Mauro
Předmět:
Zdroj: International Journal of Molecular Sciences; Apr2023, Vol. 24 Issue 7, p6684, 11p
Abstrakt: Dysfunctional phenotype of microglia, the primary brain immune cells, may aggravate Alzheimer's disease (AD) pathogenesis by releasing proinflammatory factors, such as nitric oxide (NO). The endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are bioactive lipids increasingly recognised for their essential roles in regulating microglial activity both under normal and AD-driven pathological conditions. To investigate the possible impact of chronic exposure to β-amyloid peptides (Aβ) on the microglial endocannabinoid signalling, we characterised the functional expression of the endocannabinoid system on neonatal microglia isolated from wild-type and Tg2576 mice, an AD-like model, which overexpresses Aβ peptides in the developing brain. We found that Aβ-exposed microglia produced 2-fold more 2-AG than normal microglia. Accordingly, the expression levels of diacylglycerol lipase-α (DAGLα) and monoacylglycerol lipase (MAGL), the main enzymes responsible for synthesising and hydrolysing 2-AG, respectively, were consistently modified in Tg2576 microglia. Furthermore, compared to wild-type cells, transgenic microglia basally showed increased expression of the cannabinoid 2 receptor, typically upregulated in an activated proinflammatory phenotype. Indeed, following inflammatory stimulus, Aβ-exposed microglia displayed an enhanced production of NO, which was abolished by pharmacological inhibition of DAGLα. These findings suggested that exposure to Aβ polarises microglial cells towards a pro-AD phenotype, possibly by enhancing 2-AG signalling. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje