Working Paper Article Version 1 This version is not peer-reviewed

Indispensable CBR1 in Major Depressive Disorder Therapy by Functionalized Solid Lipid Nanoparticles

Version 1 : Received: 1 July 2019 / Approved: 3 July 2019 / Online: 3 July 2019 (12:03:31 CEST)

How to cite: He, X.; Yang, L.; Wang, Z.; Jing, G.; Huang, R.; Xu, Z.; Wang, S.; Zhu, R. Indispensable CBR1 in Major Depressive Disorder Therapy by Functionalized Solid Lipid Nanoparticles. Preprints 2019, 2019070066 He, X.; Yang, L.; Wang, Z.; Jing, G.; Huang, R.; Xu, Z.; Wang, S.; Zhu, R. Indispensable CBR1 in Major Depressive Disorder Therapy by Functionalized Solid Lipid Nanoparticles. Preprints 2019, 2019070066

Abstract

Nanoparticles offer available tools for MDD research. In this assay, we applied CBR1 (cannabinoid receptor 1) knockout (CB1-/-) mice to study whether functionalized solid lipid nanoparticles loading with curcumin and dexanabinol (Cur/SLNs-HU-211) exhibited anti-depressant outcomes through CBR1. Wild-type (CB1+/+) animals together with CBR1 knockout (CB1-/-) animals received daily injections of Corticosterone (CORT) for 3 weeks to obtain MDD mice model, and then the therapeutic action of Cur/SLNs-HU-211 were evaluated, respectively. Our work show that Cur/SLNs-HU-211 nanoparticles in the existence of CBR1 facilitate an efficient motor function improvement in CORT-induced MDD mice model. Cur/SLNs-HU-211 nanoparticles alleviated symptoms on CB1+/+ MDD mice and resulted in dopamine and norepinephrine recovery following CORT-induced neurotoxicity. In conclusion, the possible mechanisms underlying the antidepressant effect of Cur/SLNs-HU-211 might be the induction of CB1 expression and downstream RASGEF1C and Egr1 expression, together with a significantly upregulation of neuron-specific genes in CB1+/+ mice only. In conclusion, CBR1 is necessary during the process of antidepressant activities of Cur/SLNs-HU-211 nanoparticles. This study confirms that Cur/SLNs-HU-211 nanoparticles based CBR1 in vivo targeting would be a potentially feasible and safe way to motivate future therapeutic strategies of Major Depressive Disorder.

Subject Areas

major depressive disorder; functionalized solid lipid nanoparticles; CBR1

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