Biology subjects

Yasrebi, A.

Publications and source records attributed to Yasrebi, A..

3 recordsLinked to original sources

bioRxiv2026

Perinatal Exposure to Organophosphate Flame Retardants Induces Sex- and Hormone-Dependent Alterations in Anxiety, Memory, Neurotransmitter Content, and Hippocampal Gene Expression

Developmental exposure to organophosphate flame retardants (OPFRs) is a public health concern due to their endocrine-disrupting potential. We examined perinatal exposure to tris(1,3-dichloro-2-propyl) phosphate, triphenyl phosphate, and tricresyl phosphate in mice. Adult male and female offspring were assessed for memory and anxiety-like behavior. Dopamine and norepinephrine were quantified in the hippocampus and prefrontal cortex (PFC), and bulk RNA sequencing was conducted for the hippocampus. OPFR-treated females in high ovarian hormone states spent less time in the open field test (OFT) center, the Y-maze unknown arm, and with the displaced object in spatial object recognition (SOR) indicating increased anxiety-like behavior and impaired spatial memory. These females also illustrated improved memory on the short-term Barnes maze, and a trending improvement in the novel object recognition test. Females in low ovarian hormone states, demonstrated a trend in center OFT exploration. OPFR-treated males displayed disruption in memory in the SOR and the short- and long-term Barnes maze. Perinatal OPFR reduced hippocampal dopamine in males and altered prefrontal dopamine in females in a hormone-dependent manner. OPFR-treated females in high ovarian hormones states demonstrated a trending decrease in PFC norepinephrine. Perinatal OPFR treatment caused differential gene expression in 121 individual genes and alteration to functional modules related to RNA processing, cellular metabolism, and extracellular organization. Hormone status also affected gene OPFR-induced altered expression, with similarity between males and high ovarian hormone state females. Our findings suggest that perinatal OPFR exposure causes widespread, sex specific, and hormone dependent disruptions in behavior, neurochemistry, and gene expression in adulthood. HighlightsO_LIAnxiety-like behavior in OPFR-treated females varied with ovarian hormone status C_LIO_LIHigh ovarian hormone OPFR females showed task-dependent changes in memory C_LIO_LIMales displayed impaired spatial memory following perinatal OPFR treatment C_LIO_LIPerinatal OPFR modifies hippocampal and prefrontal dopamine and norepinephrine C_LIO_LIOPFR treatment altered individual gene and functional gene module expression C_LI

pharmacology and toxicology↗

bioRxiv2025

PERINATAL ORGANOPHOSPHATE FLAME RETARDANT EXPOSURE ALTERS ADULT HPA AXIS FUNCTION AND AVOIDANCE BEHAVIOR IN A SEX-SPECIFIC MANNER IN MICE

Organophosphate flame retardants (OPFRs) are ubiquitous flame-retardant additives with endocrine-disrupting properties. Despite increasing evidence that OPFRs impact neurodevelopment, their effects on the neuroendocrine stress response remain poorly understood. To examine their long-term impact on stress regulation, we treated pregnant C57Bl/6J dams to a mixture of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), triphenyl phosphate (TPP), and tricresyl phosphate (TCP; 1 mg/kg each) from gestational day (GD) 7 through postnatal day (PND) 14. Adult offspring (8-9 weeks of age) were then challenged with acute stressors, including 1 h restraint or a 6-day acute variable stress (AVS) paradigm. Perinatal OPFR exposure produced persistent, sex-specific alterations in the hypothalamic-pituitary-adrenal (HPA) axis and stress-related neurocircuitry. Following 1 h restraint, OPFR-treated females showed heightened serum corticosterone. In addition, gene expression analysis revealed sex-dependent disruptions in key stress-regulatory pathways after OPFR treatment and 1 h restraint in the hypothalamus (Crhr1, Crhr2, Ptpn5) and pituitary (Crhr1, Pomc, Nr3c1). Females demonstrated more differences in adrenal gene expression related to steroidogenesis (Mc2r, Cyp11b2) and catecholamine biosynthesis (Dbh, Pnmt), with OPFR-treated groups having blunted responses. OPFR AVS females displayed reduced corticosterone and Crh mRNA in the hypothalamus, and downregulated Pacap/Pac1r expression in the bed nucleus of the stria terminalis (BNST), accompanied by increased behavioral avoidance and immobility. In males, OPFR exposure led to increased BNST Pacap and Pac1r, expression, along with hyperactivity and avoidance behaviors. Together, these findings demonstrate that early-life OPFR exposure induces lasting, sex-specific dysregulation of the HPA axis and associated stress circuits, highlighting OPFRs as developmental neuroendocrine disruptors with implications for mood and stress-related disorders.

neuroscience↗

bioRxiv2024

The Interaction Of Diet-Induced Obesity And Chronic Stress In A Mouse Model Of Menopause

Menopause is characterized by the cessation of ovarian hormone production. During postmenopause, cisgender women face increased risks of obesity, cognitive decline, and mood disorder. Mood disorders are associated with exposure to chronic stress. We investigated the combined effects of a high-fat diet (HFD) and chronic stress exposure in a mouse model of menopause using 4-vinylcyclohexene diepoxide (VCD), a selective ovotoxicant that gradually depletes ovarian follicles and hormones. Starting at 6 months, 82 female WT C57BL/6J mice received saline or VCD (130 mg/kg i.p.) 5 days per week for 3 weeks. One month after injection, mice were fed either low-fat diet (LFD) or HFD for 8 weeks followed by 6 weeks of chronic variable mild stress (CVMS). Post-CVMS, mice were either processed for gene expression of the anterodorsal BNST or behavior tests to assess cognitive and anxiety-related behaviors. Plasma samples were collected to analyze metabolic hormones and corticosterone levels. VCD-treated HFD-fed mice had higher fat and body mass, and elevated fasting glucose levels compared to controls and more pronounced avoidance behaviors and cognitive impairments. LFD-fed, VCD-treated mice exhibited less exploration of novel objects and open spaces compared to OIL and HFD counterparts. VCD elevated corticosterone levels on LFD and increased BNST Pacap gene expression on HFD. These findings highlight cognitive repercussions of estrogen deficiency and suggest a potential protective effect of a HFD against some of the adverse outcomes associated with menopause. Our study emphasizes the importance of considering dietary and hormonal interactions in the development of therapeutic strategies.

neuroscience↗