Molecular and cellular mechanisms underlying brain region-specific endocannabinoid system modulation by estradiol across the rodent estrus cycle.
Prog Mol Biol Transl Sci
; 195: 27-45, 2023.
Article
em En
| MEDLINE
| ID: mdl-36707154
ABSTRACT
Neurological crosstalk between the endocannabinoid and estrogen systems has been a growing topic of discussion over the last decade. Although the main estrogenic ligand, estradiol (E2), influences endocannabinoid signaling in both male and female animals, the latter experiences significant and rhythmic fluctuations in E2 as well as other sex hormones. This is referred to as the menstrual cycle in women and the estrus cycle in rodents such as mice and rats. Consisting of 4 distinct hormone-driven phases, the rodent estrus cycle modulates both endocannabinoid and exogenous cannabinoid signaling resulting in unique behavioral outcomes based on the cycle phase. For example, cannabinoid receptor agonist-induced antinociception is greatest during proestrus and estrus, when circulating and brain levels of E2 are high, as compared to metestrus and diestrus when E2 concentrations are low. Pain processing occurs throughout the cerebral cortex and amygdala of the forebrain; periaqueductal grey of the midbrain; and medulla and spine of the hindbrain. As a result, past molecular investigations on these endocannabinoid-estrogen system interactions have focused on these specific brain regions. Here, we will bridge regional molecular trends with neurophysiological evidence of how plasma membrane estrogen receptor (ER) activation by E2 leads to postsynaptic endocannabinoid synthesis, retrograde signaling, and alterations in inhibitory neurotransmission. These signaling pathways depend on ER heterodimers, current knowledge of which will also be detailed in this review. Overall, the aim of this review article is to systematically summarize how the cannabinoid receptors and endocannabinoids change in expression and function in specific brain regions throughout the estrus cycle.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endocanabinoides
/
Estradiol
Limite:
Animals
Idioma:
En
Revista:
Prog Mol Biol Transl Sci
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Canadá