Biology subjects

Saferin, N.

Publications and source records attributed to Saferin, N..

4 recordsLinked to original sources

bioRxiv2026

Prenatal circadian rhythm disruption induces sex-specific substance use and mood-related phenotypes in mice

20% of Americans are at risk for environmental circadian rhythm disruptions (CRD) due to shift work, leading to substantial negative health outcomes. However, females are especially affected with greater vulnerability for substance use (SU) and adverse outcomes associated with pregnancy, including for offspring at birth and later in life. In mice, prenatal CRD (pCRD) recapitulates these risks, but it is unknown whether pCRD affects SU in mature offspring. To investigate this, C57BL/6J dams were disrupted by reversing the light/dark cycle during gestation. Following pCRD, reward- (cocaine conditioned place preference, intravenous self-administration) and mood-related behaviors (open field, elevated plus maze, light/dark box, forced swim) were measured in adult offspring. Adult female offspring of dams exposed to CRD developed an anhedonic-like phenotype with decreased food self-administration, cocaine intake and reinforcing properties of cocaine. Opposingly, pCRD male offspring showed a SU-like phenotype with increased cocaine preference, higher order food self-administration and cocaine reinforcement. Interestingly, these divergent behavioral outcomes were not specific to reward. While female pCRD mice showed increased anxiety-like behavior, pCRD males showed decreased anxiety/increased risk-taking behavior, as well as decreased immobility in the forced swim test. Rhythms in corticosterone were also sex-specifically affected by pCRD. These results suggest that pCRD may predispose individuals to distinct psychiatric disorders based on sex with mood disorders developing in females and SU disorders developing in males. By better understanding how disrupted rhythms during pregnancy affect behavior in adulthood, we can develop novel therapeutic approaches for SU and mood disorders in adults.

neuroscience↗

bioRxiv2025

Dynamic encoding of valence by the anterior cingulate cortex in mice

Fear supports survival by linking environmental cues with potential threats, but its dysregulation contributes to anxiety disorders and PTSD. While the contributions of hippocampus and amygdala to fear memory are well established, the role of the anterior cingulate cortex (ACC) during and after acquisition remains less clear. Here we longitudinally recorded ACC neuronal activity using single-photon calcium imaging in freely behaving mice undergoing auditory fear conditioning. During cue pre-exposure, neural responses to the cue were strongest to early novel presentations and declined with repetition. During acquisition, responses emerged late in training as the cue became shock-predictive. Ensemble analysis identified subpopulations of "freezing on" and "freezing off" cells in the ACC whose activation coincided with decreased neural activity and increased neural synchrony. During 24-h and 48-h recall, ACC responses were robust to early presentations but diminished during late tones; similarly, a subpopulation of neurons emerged that was upmodulated by the CS in early 24-h and 48-h recall. Together, our results demonstrate that ACC neuronal response to a cue reorganizes both within and across sessions, with dynamic changes in population activity, recruitment, and synchrony that mirror changes in novelty and negative valence. This pattern suggests a role for ACC as a flexible hub that dynamically represents changes in cue significance.

neuroscience↗

bioRxiv2024

Folate prevents the autism-related phenotype caused by developmental pyrethroid exposure in prairie voles

Neurodevelopmental disorders (NDDs) have dramatically increased in prevalence to an alarming one in six children, and yet both causes and preventions remain elusive. Recent human epidemiology and animal studies have implicated developmental exposure to pyrethroid pesticides, one of the most common classes of pesticides in the US, as an environmental risk factor for autism and neurodevelopmental disorders. Our previous research has shown that low-dose chronic developmental pyrethroid exposure (DPE) changes folate metabolites in the adult mouse brain. We hypothesize that DPE acts directly on molecular targets in the folate metabolism pathway, and that high-dose maternal folate supplementation can prevent or reduce the biobehavioral effects of DPE. We exposed pregnant prairie vole dams chronically to vehicle or low-dose deltamethrin (3 mg/kg/3 days) with or without high-dose folate supplementation (methylfolate, 5 mg/kg/3 days). The resulting DPE offspring showed broad deficits in five behavioral domains relevant to neurodevelopmental disorders (including the social domain); increased plasma folate concentrations; and increased neural expression of SHMT1, a folate cycle enzyme. Maternal folate supplementation prevented most of the behavioral phenotypes (except for repetitive behaviors) and caused potentially compensatory changes in neural expression of FOLR1 and MTHFR, two folate-related proteins. We conclude that DPE causes neurodevelopmental disorder-relevant behavioral deficits; DPE directly alters aspects of folate metabolism; and preventative interventions targeting folate metabolism are effective in reducing, but not eliminating, the behavioral effects of DPE.

neuroscience↗

bioRxiv2023

Developmental pyrethroid exposure disrupts folate metabolism in mouse brain

Environmental and genetic risk factors, and their interactions, contribute significantly to the etiology of neurodevelopmental disorders (NDDs). Recent epidemiology studies have implicated pyrethroid pesticides as an environmental risk factor for autism and developmental delay. Our previous research showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice caused male-biased changes in the brain and in NDD-relevant behaviors in adulthood. Here, we used a metabolomics approach to determine the broadest possible set of metabolic changes in the adult male mouse brain caused by low-dose pyrethroid exposure during development. Using a litter-based design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood and collected whole brain samples for untargeted high-resolution metabolomics analysis. Developmentally exposed mice had disruptions in 116 metabolites which clustered into pathways for folate biosynthesis, retinol metabolism, and tryptophan metabolism. As a cross-validation, we integrated metabolomics and transcriptomics data from the same samples, which confirmed previous findings of altered dopamine signaling. These results suggest that pyrethroid exposure during development leads to disruptions in metabolism in the adult brain, which may inform both prevention and therapeutic strategies. HighlightsO_LIDevelopmental pyrethroid exposure disrupts brain metabolism in adulthood C_LIO_LIExposure disrupts metabolic pathways for folate, retinol, and tryptophan C_LIO_LIExposure disrupts genetic and metabolic pathways for dopamine signaling C_LI

neuroscience↗