Biology subjects

Cortes, L. R.

Publications and source records attributed to Cortes, L. R..

2 recordsLinked to original sources

bioRxiv2021

DNA methylation and demethylation underlie the sex difference in estrogen receptor alpha in the arcuate nucleus

IntroductionNeurons expressing estrogen receptor (ER) in the arcuate nucleus (ARC) of the hypothalamus sex-specifically control energy homeostasis and bone density. Females have more of these neurons than do males, but how this sex difference develops is unknown. ObjectiveWe tested the hypothesis that DNA methylation and/or demethylation control the development of a sex difference in ER in the ARC. MethodsER immunoreactive neurons were quantified at birth and at weaning in male, female and testosterone-treated female mice that received neonatal, intracerebroventricular injections of vehicle or zebularine, a DNA methyltransferase inhibitor. Methylation status of Esr1 was determined in the ARC and ventromedial hypothalamus (VMH) using bisulfite conversion of DNA followed by pyrosequencing. Small interfering RNAs against ten-eleven translocases were used to examine effects of demethylation on ER cell number. ResultsA sex difference in ER cell number in the ARC, favoring females, developed between birth and weaning and was due to programming effects of testosterone. Zebularine treatment eliminated the sex difference in ER in the ARC at weaning by decreasing ER in females to male-like levels. Previously, the same treatment increased ER in males in the VMH. A promoter region of Esr1 exhibited sex differences in opposite directions in percent of total methylation in the ARC (females > males) and VMH (males > females). Moreover, neonatal inhibition of demethylation increased ER in the ARC of males. ConclusionDNA methylation and demethylation regulate ER cell number in the ARC, and methyl marks may paradoxically activate Esr1 in this region.

neuroscience↗

bioRxiv2019

Extended access self-administration of methamphetamine is associated with age- and sex-dependent differences in drug taking behavior and recognition memory deficits in rats

Individuals who begin drug use during early adolescence experience more adverse consequences compared to those initiating later, especially if they are female. The mechanisms for these age and gender differences remain obscure, but studies in rodents suggest that psychostimulants may disrupt the normal ontogeny of dopamine and glutamate systems in the prefrontal cortex (PFC). Here, we studied Sprague-Dawley rats of both sexes who began methamphetamine (METH, i.v.) self-administration (SA) in adolescence (postnatal [P] day 41) or adulthood (P91). Rats received seven daily 2-h SA sessions with METH or saccharin as the reinforcer, followed by 14 daily long access (LgA; 6 h) sessions. After 7 and 14 days of abstinence, novel object (OR) or object-in-place (OiP) recognition was assessed. PFC and nucleus accumbens were collected 7 days after the final cognitive test and NMDA receptor subunits and dopamine D1 receptor expression was measured. We found that during LgA sessions, adolescent-onset rats escalated METH intake more rapidly than adult-onset rats, with adolescent-onset females earning the most infusions. Adolescent-onset rats exhibited modest deficits in OiP compared to adult-onset rats, but there was no sex difference in this effect and no groups differed in OR. We found no group differences in D1 and NMDA receptor expression, suggesting no long-lasting alteration of ontogenetic expression profiles. Our findings suggest that adolescent-onset drug use is more likely to lead to compulsive-like patterns of drug-taking and subsequent dysfunction of PFC-dependent cognition.

neuroscience↗