Premium
Effects of a WIN 55,212‐2‐based therapy in two mouse models of Alzheimer's disease
Author(s) -
Schmitt Franziska,
Bayer Thomas A,
Ott Frederik W,
Bouter Yvonne
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043211
Subject(s) - endocannabinoid system , neuroprotection , cannabinoid receptor , cannabinoid , pharmacology , morris water navigation task , cannabinoid receptor type 2 , neuroscience , medicine , receptor , chemistry , psychology , hippocampus , agonist
Background Limited therapeutic effects of current Alzheimer treatments highlight the need for new research approaches. Targeting the endocannabinoid system could be such an approach. The endocannabinoid system plays a role in brain development, memory formation, and presynaptic activity as well as in neuro‐inflammatory processes and neuroprotection (Mechoulam et al., 2014; Salzet et al., 2000). Several in vitro studies showed that cannabinoids could stimulate phagocytosis and degradation of Aβ as well as stimulate the removal of intraneuronal Aβ in vitro (Currais et al., 2016). The current study aims to investigate the therapeutic potential of a WIN‐based Alzheimer’s disease therapy using mouse models of sporadic (Tg4‐42; Bouter et al., 2013) and familial (5xFAD; Oakley et al., 2006) Alzheimer’s disease. WIN 55,212‐2 (WIN) is a synthetic cannabinoid binding more efficiently to CB1 and CB2 receptors than Tetrahydrocannabinol. Method Tg4‐42 and 5XFAD mice were treated by intraperitoneal injections with the synthetic cannabinoid WIN 55,212‐2 (0,2mg/kg) over a period of 42 days. Sex‐ and age‐matched control groups are treated with vehicle solution (5% ethanol, 5% Tween80 in 0,9% sodium chloride solution). Spatial reference memory was assessed using the Morris water maze, motor performance with the Rotarod and anxiety behavior was evaluated using the elevated plus‐maze and the dark‐light box. 5xFAD mice carry five mutations strongly linked to amyloid processing. The effects of WIN on the Aβ pathology in 5XFAD mice will be investigated using immunohistochemistry and presented. Result WIN 55,212‐22 treatment of Tg4‐42 mice showed increased spatial reference memory and increased motor performance in comparison to the control group. Preliminary data analysis of 5xFAD mice shows significant results pointing in the same direction. Analysis of 5xFAD mice will be completed and presented. Conclusion Our findings reinforce a cannabinoid‐based therapy as a promising strategy for treating Alzheimer’s disease with WIN 55,212‐22 as a possible candidate.