Differences in the co-distribution of the Cannabinoid Receptor-1, FAAH, and MAGL in the human and mouse brain could be limiting clinical translation of endocannabinoid outcomes in mouse models of Alzheimer disease.
Heistad, R. M.; Nyarko, J. N. K.; Pennington, P. R.; Saeed, H.; Gomes, L. V. B.; Mousseau, D. D.
Show abstract
Endocannabinoid system (ECS) outcomes in mouse models of Alzheimer disease (AD) do not always align with the clinical disease course. We compared the distribution of the Cannabinoid Receptor-1 (CB1R) and the enzymes, FAAH and MAGL, in autopsy AD brain samples as well as in the J20 (hAPPSwe/Ind) mouse model of AD. Both sources revealed several anti-CB1R immunoreactive species, e.g. one at 47-kDa (corresponding to the protein-coding sequence) and a reported putative splice variant at 37 kDa. We did not observe any changes in the mean expression in CB1R, FAAH or MAGL in the human samples, but did observe sex- and genotype-specific changes in the mouse brain. Regression analysis revealed strong sex- and APOE {varepsilon}4-dependent associations among the CB1Rs as well as between CB1Rs and MAGL (but not FAAH) in human cortical (but not hippocampal) samples. In the J20 mouse, associations between CB1Rs were limited to hippocampal samples, whereas associations between CB1R and both MAGL and FAAH were observed in the cortex. A diagnosis of AD disrupted any associations in the human dataset, whereas in several instances, the associations were enhanced by the hAPPSwe/Ind transgene. This inferred species-dependent regulation of the ECS could impact the clinical translational of ECS outcomes in preclinical models of AD pathology.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Integrative Brain Transcriptome Analysis Links Complement Component 4 and HSPA2 to the APOE ε2 Protective Effect in Alzheimer Disease 95%
- Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease 95%
- Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer’s disease 94%
Similar papers in this journal
- Cystatin F (Cst7) drives sex-dependent changes in microglia in an amyloid-driven model of Alzheimer's Disease 94%
- Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model 94%
- Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models 93%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.