Ontogeny and programming of the fetal temporal cortical endocannabinoid system by moderate maternal nutrient reduction in baboons ( Papio spp.)

Abstract

Poor nutrition during pregnancy is a worldwide public health problem. Maternal nutrient reduction ( MNR ) is associated with maternal and fetal stress and a sex‐dependent decrease in nonhuman primate ( NHP ) cognitive performance. Early life stress potentiates epileptogenesis in a sex‐specific manner, and temporal lobe ( TL ) epilepsy is associated with neurocognitive disorders. The endogenous cannabinoid system ( ECS ) demonstrates remarkable developmental changes and plays a key role in aging‐related diseases (e.g., dementia). Baboons have been studied as a natural model of epilepsy and express all ECS system components. We therefore evaluated baboon fetal temporal cortex ECS ontogenic and MNR ‐dependent changes. At 120 days gestational age ( dGA ) (term 185 days), maternal, fetal, and placental morphometry were similar between control and MNR pregnancies. MNR maternal weight gain was decreased compared with controls at 165 dGA independent of fetal sex. In male fetuses, expression of ECS synthesizing and degrading enzymes was gestational age‐dependent, with the exception of fatty acid amide hydrolase ( FAAH ). MNR had a sex‐specific effect on the protein expression of CB 1R during development: CB 1R protein expression was decreased in fetal temporal cortex of male fetuses at 120 and 140 dGA . Our data reveal that the MNR has sex‐specific effects on temporal cortical expression of the ECS in baboon offspring and shows vulnerability of ECS in male fetuses during gestation.

Cannabinoid CB2 receptor orthologues; in vitro function and perspectives for preclinical to clinical translation

“…Rhesus macaque ( Macaca mulatta ) CB 2 has 97% identity with hCB 2 and has been utilised to evaluate PET ligands (e.g., Attili et al, 2019). Limited in vivo and/or ex vivo characterisation of CB 2 receptor function and/or expression is also available for zebrafish ( Danio rerio ; Rodriguez‐Martin et al, 2007; Sufian et al, 2019), goldfish ( Carassius auratus ; Cottone et al, 2013), chicken ( Gallus gallus ; e.g., Khodadadi et al, 2017), vole ( Microtus ; Simmons et al, 2021), guinea pig ( Cavia porcellus ; e.g., Giannini et al, 2008), pig ( Sus scrofa ; Pirino et al, 2018), dog ( Canis familiaris ; dCB 2 ; e.g., Rossi et al, 2020), sheep ( Ovis aries ; Tsutahara et al, 2011), cow ( Bos taurus ; e.g., Dall'Aglio et al, 2017), horse ( Equus caballus ; e.g., Kupczyk et al, 2022), vervet monkey ( Chlorocebus pygerythurus ; e.g., Bouskila et al, 2016) and baboon ( Papio ; e.g., Gandhi et al, 2019).…”