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Effects of tetrahydrocannabinol treatment on brain metabolism and neuron loss in a mouse model of sporadic Alzheimer's disease
27 March 2019 (online)
Limited therapeutic effects of current Alzheimer's diesease (AD) treatments highlight the need for new research approaches. The endocannabinoid system plays a role in neuroinflammation and memory formation and therefore adresses major pathological hallmarks of AD. The Tg4 – 42 mouse model of sporadic AD develops severe neuron loss in the hippocampus in correlation to intraneuronal Abeta expression. The aim of the present study was the characterization of changes in brain metabolism of Tg4 – 42 mice and the evaluation of the therapeutic effect of tetrahydrocannabinol (THC) treatment in vivo monitored by 18F-FDG-PET.
Transgenic Tg4 – 42 mice expressing human Abeta 4 – 42 were treated with THC for six weeks starting at three months of age. Quantification of neuron numbers was performed with unbiased sterology at 7 months. Young and aged Tg4 – 42, wildtype and THC-treated mice were scanned with 18F-FDG-PET/MRI and quantification of brain regions was performed.
18F-FDG-PET detected significantly reduced cerebral glucose metabolism in aged Tg4 – 42 mice compared to young Tg4 – 42 and wildtype mice. THC-treatment reduces hippocampal neuron loss in Tg4 – 42 mice compared to controls and restores cerebral glucose metabolism in the hippocampus.
Tg4 – 42 mice display an age-dependent altert glucose metabolism accompanied by severe neuron loss in the hippocampus. 18F-FDG-PET displays cerebral changes and monitors therapeutic effects in vivo. THC-treatment reduces hippocampal neuron loss improving regional brain metabolism. Therefore, alterations of the endocnnabinoid system with THC display an interesting therapeutic approach in AD.