Biology subjects

Lapp, H. E.

Publications and source records attributed to Lapp, H. E..

4 recordsLinked to original sources

bioRxiv2025

Sex Differences in B2 SINE RNA Expression and its Role in Hippocampal Development

Once dismissed as "junk", transposable elements (TE) have recently gained recognition for their regulatory roles, notably in the brain and in development. The brain is hormone-responsive and the hippocampus in particular is sensitive to circulating gonadal hormones. While transcriptionally active, TE function remains poorly understood, especially in the brain. We and others have shown that one particular TE RNA, B2 SINE ncRNA, is a regulator in the rodent hippocampus, especially after a psychologically stressful event like acute restraint stress. It is unknown, however, if B2 SINE ncRNA is necessary for the proper development of hippocampal neurons, and furthermore, if there is a sex difference in this development. This work investigates the difference in expression of B2 SINE RNA across sexes and its role in the development of primary hippocampal neurons. We utilized pooled locked nucleic acid (LNA) GapmeRs to knock down the expression of B2 SINE RNA and treated primary hippocampal neurons with dihydrotestosterone (DHT) to test if there is a difference in dendritic complexity. We used Sholl analysis to quantify the branching, number of tips, and Sholl mean. We found a sex difference in both B2 SINE, higher in males compared to females, and {beta}-actin, lower in males compared to females. Additionally, knocking down B2 SINE RNA results in a reduction of dendritic complexity in male but not in female neurons. Taken together, this work suggests that B2 SINE RNA is expressed differentially and plays an important role in the proper development of hippocampal neurons in a sex dependent manner. Our findings support the identification of a sex-specific biomarker that may enable individualized treatment of conditions influenced by sex. This is the first evidence of the role a transposable elements RNA has in the regulation of the development of neurons and the first to show that differential regulation by sex. Summary ParagraphLong considered "junk DNA", transposable elements have gained recognition as regulators in the genome. Some of these elements are transcriptionally active and have been known to control the expression of downstream protein coding genes. Recently, murine B2 SINE RNA has been shown to regulate glucocorticoid responsive genes in the rodent hippocampus. However, it is unknown if B2 SINE RNA is necessary for the proper development of hippocampal neuron structure and if there is a sex difference in this development. Here we show that B2 SINE is higher in the male hippocampus compared to females, and knocking down B2 SINE RNA results in a reduction of dendritic complexity in male but not in female neurons. This work shows that B2 SINE RNA is expressed differentially across sexes, and that this noncoding RNA plays an important role in the development of hippocampal neurons. These findings are the first to demonstrate the role for a transposable elements RNA in the development of neuronal structure and the first to show that this is differential across sex. These findings support the identification of a sex specific biomarker that could lead to individual treatments of neurological disorders influenced by sex.

neuroscience↗

bioRxiv2025

Postnatal maternal care impacts hypothalamic Esrrg gene expression, co-expression profiles, and the DNA methylome in prenatal bisphenol-exposed rats

BackgroundEnvironmental exposures co-occurring during early life have a profound influence on neurodevelopment. Our previous work in rats suggests that postnatal maternal care modulates the effects of prenatal exposure to bisphenols, an estrogenic endocrine disrupting chemical, on offspring neurodevelopment. Elevated maternal licking/grooming and prenatal bisphenol exposure have opposing effects on estrogen receptor expression in the medial preoptic area (MPOA), which could impact expression of estrogen-responsive genes. We hypothesized that maternal licking/grooming would mitigate the effects of prenatal bisphenol exposure on estrogen receptor signaling in the developing MPOA. In addition, we hypothesized that there would be interactive effects of prenatal bisphenol exposure and maternal licking/grooming on DNA methylation nearby estrogen responsive elements. ResultsOur results suggest that maternal licking/grooming normalized prenatal bisphenol-induced upregulation of estrogen-related receptor gamma (Esrrg) expression in female pups. These mitigating impacts were also evident in co-expression gene profiles that were enriched for estrogen-responsive genes. DNA methylation analyses indicated that maternal licking/grooming levels influenced the number of differentially methylated regions for prenatal bisphenol-exposed pups. These differentially methylated regions were enriched for binding sites for transcription factors that are known to interact with estrogen receptors. Finally, supplemental "licking-like" tactile stimulation normalized the DNA methylome in prenatal bisphenol-exposed female pups, with an increase and normalization of ESRRG binding to ESRRG-responsive genes. ConclusionsThese results identify a novel biological mechanism in which maternal licking/grooming can mitigate the negative neurodevelopmental impacts of prenatal bisphenol exposure and provides a proof-of-concept for postnatal tactile stimulation as a potential intervention strategy to improve neurodevelopmental outcomes.

genomics↗

bioRxiv2023

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes

Bisphenols (BPs), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal BP exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal BP exposure and postnatal maternal care on neurodevelopment and behavior. Our findings suggest that the effects of prenatal BP exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal BP exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal BP exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal BP exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal BP exposure and improve health and well-being in human populations.

neuroscience↗

bioRxiv2023

Automated Maternal Behavior during Early life in Rodents (AMBER) pipeline

Mother-infant interactions during the early postnatal period are critical for infant survival and the scaffolding of infant development. Rodent models are used extensively to understand how these early social experiences influence neurobiology across the lifespan. However, methods for measuring postnatal dam-pup interactions typically involve time-consuming manual scoring, vary widely between research groups, and produce low density data that limits downstream analytical applications. To address these methodological issues, we developed the Automated Maternal Behavior during Early life in Rodents (AMBER) pipeline for quantifying home-cage maternal and mother-pup interactions using open-source machine learning tools. DeepLabCut was used to track key points on rat dams (32 points) and individual pups (9 points per pup) in postnatal day 1-10 video recordings. Pose estimation models reached key point test errors of approximately 4.1-10 mm (14.39 pixels) and 3.44-7.87 mm (11.81 pixels) depending on depth of animal in the frame averaged across all key points for dam and pups respectively. Pose estimation data and human-annotated behavior labels from 38 videos were used with Simple Behavioral Analysis (SimBA) to generate behavior classifiers for dam active nursing, passive nursing, nest attendance, licking and grooming, self-directed grooming, eating, and drinking using random forest algorithms. All classifiers had excellent performance on test frames, with F1 scores above .886. Performance on hold-out videos remained high for nest attendance (F1=.990), active nursing (F1 =.828), and licking and grooming (F1=.766) but was lower for eating, drinking, and self-directed grooming (F1=.534-.554). A set of 242 videos was used with AMBER and produced behavior measures in the expected range from postnatal 1-10 home-cage videos. This pipeline is a major advancement in assessing home-cage dam-pup interactions in a way that reduces experimenter burden while increasing reproducibility, reliability, and detail of data for use in developmental studies without the need for special housing systems or proprietary software.

animal behavior and cognition↗