Biology subjects

Sia, E.

Publications and source records attributed to Sia, E..

3 recordsLinked to original sources

bioRxiv2026

Prenatal THC exposure alters metabolic gene expression and KEAP1 regulation in the mouse placental labyrinth

Introduction: Prenatal cannabinoid exposure may influence fetal development through changes in placental biology, yet its effects on metabolic gene regulation remain poorly understood. We examined the effects of {Delta}9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the mouse placental labyrinth zone. Methods: Pregnant C57BL/6JRj mice received THC (5 mg/kg), CBD (5 mg/kg), or vehicle daily by intraperitoneal injection from gestational day 5 to 17.5. Targeted NanoString profiling and pathway analysis were combined with RT-qPCR and protein measurements. Results: THC exposure reduced glutaminase (Gls), Kelch-like ECH-associated protein 1 (Keap1), and FMS-like tyrosine kinase 3 (Flt3) expression (false discovery rate = 0.0904 for each). Pathway analysis identified transcriptional changes in the nine-gene arginine-metabolism set (false discovery rate = 0.0527). No genes or pathways met the significance criteria following CBD exposure. RT-qPCR confirmed lower Keap1 expression with sexes pooled and identified lower Gls and Flt3 expression in male samples. KEAP1 protein abundance increased despite lower Keap1 mRNA, while nuclear factor erythroid 2-related factor 2 localization and heme oxygenase 1 (Hmox1) expression showed no significant differences. Discussion: These findings identify amino acid metabolic gene expression and KEAP1 regulation as complementary components of the placental response to prenatal THC exposure, connecting transcriptional changes with protein regulation within the placental exchange region.

developmental biology↗

bioRxiv2023

Repeated footshock stress induces an escalation of cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1

Stress is a significant contributor to the development and progression of substance use disorders (SUDs) and is problematic as it is unavoidable in daily life. Therefore, it is important to understand the neurobiological mechanisms that underlie the influence of stress on drug use. We have previously developed a model to examine the contribution of stress to drug-related behavior by administering a stressor, electric footshock stress, daily at the time of cocaine self-administration in rats resulting in an escalation of cocaine intake. This stress-induced escalation of cocaine intake involves neurobiological mediators of stress and reward such as cannabinoid signaling. However, all of this work has been conducted in male rats. Here we test the hypothesis that repeated daily stress can produce an escalation of cocaine in both male and female rats. We further hypothesize that cannabinoid receptor 1 (CB1R) signaling is recruited by repeated stress to influence cocaine intake in both male and female rats. Male and female Sprague-Dawley rats self-administered cocaine (0.5 mg/kg/inf, i.v.) during a modified short-access paradigm wherein the 2-hr access was separated into 4-30 min self-administration blocks separated by 4-5 min drug free period. Footshock stress produced a significant escalation of cocaine intake similarly in both male and female rats. Female stress-escalated rats did display greater time-out non-reinforced responding and greater "front-loading" behavior. In males, systemic administration of a CB1R inverse agonist/antagonist Rimonabant only attenuated cocaine intake in rats with a history of combined repeated stress and cocaine self-administration. However, in females, Rimonabant attenuated cocaine intake in the no stress control group but only at the highest dose of Rimonabant (3 mg/kg, i.p.) suggesting that females show a greater sensitivity to CB1R antagonism. However, female rats with a history of stress showed even greater sensitivity to CB1R antagonism as both doses of Rimonabant (1, 3 mg/kg) attenuated cocaine intake in stress-escalated rats similar to males. Altogether these data demonstrate that stress can produce significant changes in cocaine self-administration and suggests that repeated stress at the time of cocaine self-administration recruits CB1Rs to regulate cocaine-taking behavior across sexes.

neuroscience↗

bioRxiv2019

Ratiometric quorum sensing in bacterial conjugation

Plasmid-mediated horizontal gene transfer of antibiotic-resistance and virulence in pathogenic bacteria underlies a major public health issue. Understanding how, in the absence of antibiotic-mediated selection, plasmid-bearing cells avoid being outnumbered by plasmid-free cells, is key to developing counter strategies. Here we quantified the induction of Enterococcus faecalis plasmidial sex-pheromone pathway to show that the integration of the stimulatory (mate-sensing) and inhibitory (self-sensing) signaling modules from the pCF10 conjugative plasmid, provides a precise measure of the recipient-to-donor ratio, agnostic to variations in population size. Such ratiometric control of conjugation favors vertical plasmid-transfer under low mating likelihood and allows activation of conjugation functions only under high mating likelihood. We further show that this strategy constitutes a cost-effective investment into mating effort, as overstimulation produces unproductive self-aggregation and reductions in the growth rate. A mathematical model suggests that ratiometric control of conjugation limits the spread of antibiotic resistance in absence of antibiotics, predicting a long-term stable co-existence of donors and recipients. Our results demonstrate how population-level parameters can control transfer of antibiotic-resistance in bacteria, opening the door for biotic control strategies. Ratiometric sensing in bacteria mirrors sexual behaviors observed in eukaryotes.

microbiology↗