Neuroanatomical Analysis of Neuronal Sets That Co-express the Growth Hormone Secretagogue Receptor and the Cannabinoid Type 1 Receptor in the Mouse Brain

SAENZ, CAMILA; FERNÁNDEZ, GIMENA; DE FRANCESCO, PABLO NICOLÁS; MACKIE, KENNETH; PERELLO, MARIO

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biocencias; 2022

Sociedad Argentina de Investigación Clínica

The growth hormone secretagogue receptor (GHSR) is a G-protein coupled receptor (GPCR) highly expressed in the brain. GHSR mediates the effects of two hormones: ghrelin and liver-expressed antimicrobial peptide 2. Notably, GHSR acts via ligand-independent mechanisms, which include constitutive activity and allosteric modulation of other GPCRs. The cannabinoid receptor type 1 (CB1R) is also a GPCR highly expressed in the brain. CB1R is activated by endogenous endocannabinoids (i.e., anandamide) as well as phytocannabinoids, such as tetrahydrocannabinol (THC) the principal psychoactive cannabinoid of cannabis. Interestingly, GHSR and CB1R expression have been observed within many of the same brain nuclei, suggesting that these GPCR may act on common neuronal sets to mediate its neurobiological effects. Here, we explored the extent of this putative GHSR and CB1 interaction in the brain of male mice. To map GHSR distribution, we used two complementary approaches: 1) a fluorescent variant of ghrelin (Fr-ghrelin) and 2) a mutant mouse in which GHSR promoter drives the expression of GFP (GHSR-eGFP mice). In both cases, the presence of CB1R was visualized using a validated anti-CB1R antibody.Using the Fr-ghrelin labeling together with CB1R immunolabeling, we found that cells containing both GHSR and CB1R are mainly located in the hippocampus area, where GHSR cells were also positive for CB1R representing the 45,46 ± 7,28 % of all GHSR cells (p<0.05, one sample t-test). In brain sections of GHSR-eGFP mice inmunostained with CB1R antibody, we found cells containing both GHSR and CB1R are mainly located in the hippocampus posterior area, where GHSR cells were also positive for CB1R representing the 40,08 ± 13,33 % of all GHSR cells (p= 0.095, one sample t-test). In contrast, simultaneous presence of GHSR and CB1R was not observed elsewhere in the brain.Thus, we started to elucidate some of the neuronal populations where GHSR and CB1 may directly act.