Behavioral Studies of p62 KO Animals with Implications of a Modulated Function of the Endocannabinoid System

Autor: Christina Keller, Sebastian Rading, Laura Bindila, Meliha Karsak
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cells, Vol 11, Iss 9, p 1517 (2022)
Druh dokumentu: article
ISSN: 11091517
2073-4409
DOI: 10.3390/cells11091517
Popis: Elementary emotional states and memory can be regulated by the homeostasis of the endocannabinoid system (ECS). Links between the ECS and the autophagy receptor p62 have been found at the molecular level and in animal studies. This project aimed to validate the anxiety and memory phenotype of p62 knockout (KO) animals and whether the ECS plays a role in this. We examined the behavior of p62 KO animals and analyzed whether endocannabinoid levels are altered in the responsible brain areas. We discovered in age-dependent obese p62 KO mice decreased anandamide levels in the amygdala, a brain structure important for emotional responses. Against our expectation, p62 KO animals did not exhibit an anxiety phenotype, but showed slightly increased exploratory behavior as evidenced in novel object and further tests. In addition, KO animals exhibited decreased freezing responses in the fear conditioning. Administration of the phytocannabinoid delta9-tetrahydrocannabinol (THC) resulted in lesser effects on locomotion but in comparable hypothermic effects in p62 KO compared with WT littermates. Our results do not confirm previously published results, as our mouse line does not exhibit a drastic behavioral phenotype. Moreover, we identified further indications of a connection to the ECS and hence offer new perspectives for future investigations.
Databáze: Directory of Open Access Journals
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