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BioMed Central, Journal of Neuroinflammation, 1(12), 2015

DOI: 10.1186/s12974-015-0305-9

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Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells

Journal article published in 2015 by Rea Pihlaja, Jatta Takkinen, Olli Eskola, Jenni Vasara, Francisco R. López-Picón ORCID, Merja Haaparanta-Solin ORCID, Juha O. Rinne
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract Background Recently, the role of monoacylglycerol lipase (MAGL) as the principal regulator of simultaneous prostaglandin synthesis and endocannabinoid receptor activation in the CNS was demonstrated. To expand upon previously published research in the field, we observed the effect of the MAGL inhibitor JZL184 during the early-stage proinflammatory response and formation of beta-amyloid (Aβ) in the Alzheimer’s disease mouse model APdE9. We also investigated its effects in proinflammatory agent - induced astrocytes and microglia isolated from adult mice. Findings Transgenic APdE9 mice (5 months old) were treated with JZL184 (40 mg/kg) or vehicle every day for 1 month. In vivo binding of the neuroinflammation-related, microglia-specific translocator protein (TSPO) targeting radioligand [ 18  F]GE-180 decreased slightly but statistically non-significantly in multiple brain areas compared to vehicle-treated mice. JZL184 treatment induced a significant decrease in expression levels of inflammation-induced, Iba1-immunoreactive microglia in the hippocampus ( P