Details

Autor(en) / Beteiligte

• Gonzalo-Consuegra, Claudia
• Santos-García, Irene
• García-Toscano, Laura
• Martín-Baquero, Raquel
• Rodríguez-Cueto, Carmen
• Wittwer, Matthias B.
• Dzygiel, Pawel
• Grether, Uwe
• de Lago, Eva
• Fernández-Ruiz, Javier

Titel

Involvement of CB1 and CB2 receptors in neuroprotective effects of cannabinoids in experimental TDP-43 related frontotemporal dementia using male mice

Ist Teil von

• Biomedicine & pharmacotherapy, 2024-05, Vol.174, p.116473-116473, Article 116473

Ort / Verlag

Elsevier Masson SAS

Erscheinungsjahr

2024

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The elevation of endocannabinoid levels through inhibiting their degradation afforded neuroprotection in CaMKIIα-TDP-43 mice, a conditional transgenic model of frontotemporal dementia. However, which cannabinoid receptors are mediating these benefits is still pending to be elucidated. We have investigated the involvement of the CB1 and the CB2 receptor using chronic treatments with selective ligands in CaMKIIα-TDP-43 mice, analysis of their cognitive deterioration with the Novel Object Recognition test, and immunostaining for neuronal and glial markers in two areas of interest in frontotemporal dementia. Our results confirmed the therapeutic value of activating either the CB1 or the CB2 receptor, with improvements in the animal performance in the Novel Object Recognition test, preservation of pyramidal neurons, in particular in the medial prefrontal cortex, and attenuation of glial reactivity, in particular in the hippocampus. In addition, the activation of both CB1 and CB2 receptors reduced the elevated levels of TDP-43 in the medial prefrontal cortex of CaMKIIα-TDP-43 mice, an effect exerted by mechanisms that are currently under investigation. These data reinforce the notion that the activation of CB1 and CB2 receptors may represent a promising therapy against TDP-43-induced neuropathology in frontotemporal dementia. Future studies will have to confirm these benefits, in particular with one of the selective CB2 agonists used here, which has been thoroughly characterized for clinical development. [Display omitted] •Cannabinoids are neuroprotective in experimental TDP-43-dependent FTD.•Activating the CB1 receptor confirmed these benefits.•Similar benefits were found after activating the CB2 receptor.•Benefits appear to involve the control of glial reactivity.•A possible reduction in TDP-43 levels may also be involved.