Phenotypic changes in cortical astrocytes translatome across the estrous cycle
Astroglia have recently been implicated in various functions in the brain including modulating neuronal network functions, forming components of the blood brain barrier, and responding to neuroinflammation. Indeed, the neocortex contains neuronal circuits responsible for mediating complex higher-order behaviours and astroglia have recently been implicated in modulating neocortical behaviours. Neocortical astroglia express gonadal hormone receptors and respond to alterations in circulating gonadal hormones, which readily access the brain, with changes in function as well as protein and gene expression. In female rodents, circulating levels of estrogen and progesterone fluctuate across the estrous cycle and these cyclic changes might be expected to alter astroglia function. While some work has characterized astroglial protein expression changes during the estrous cycle in the cortex, no one has examined changes in active gene translation in astroglia across the estrous cycle. We use translating ribosome affinity purification with RNA sequencing (TRAPseq) to characterize the astroglial translatome in adult female mice during metestrus, proestrus, and estrus and compared it with that of male mice. We find the largest differences in the translatome between proestrus and estrus, and that males and females on metestrus cluster closely together, suggesting the neocortical astroglial translatome is responsive to circulating gonadal hormones. Additionally, neuroplastic processes are amongst the top gene ontologies called when examining differentially expressed genes between the different days of the cycle and between the days of the cycle. This suggests that cortical astrocyte phenotypes are rapidly modified across the estrous cycle, which may influence neocortical neuronal network function. Overall design: RNA sequencing on astrocytes mRNA prepared using translating ribosome affinity purification (TRAP) from male and female B6;FVB-Tg(Aldh1l1-EGFP/Rpl10a)JD130Htz/J mice. Female mice were collected at 09:00 during different days of the estrous cycle (metestrus, proestrus, estrus).