Biology subjects

Gayden, J.

Publications and source records attributed to Gayden, J..

3 recordsLinked to original sources

bioRxiv2024

Regulation of Fentanyl Reward in Male and Female Mice by the Circadian Transcription Factor NPAS2

Synthetic opioids like fentanyl are highly potent and prevalent in the illicit drug market, leading to tolerance, dependence, and opioid use disorder (OUD). Chronic opioid use disrupts sleep and circadian rhythms, which persist even during treatment and abstinence, increasing the risk of relapse. The bodys molecular clock, regulated by transcriptional and translational feedback loops, controls various physiological processes, including the expression of endogenous opioids and their receptors. The circadian transcription factor NPAS2, highly expressed in the nucleus accumbens, may have a crucial function in opioid-related behaviors. Our study found sex-specific roles for NPAS2-mediated reward behaviors in male and female mice, including in fentanyl seeking and craving. We also identified specific cell types and transcriptional targets in the nucleus accumbens of both mice and humans by which NPAS2 may mediate the impact of fentanyl on brain physiology and in opioid reward-related behaviors. Ultimately, our findings begin to uncover the mechanisms underlying circadian rhythm dysfunction and opioid addiction.

neuroscience↗

bioRxiv2023

Three-dimensional characterization of medium spiny neuron heterogeneity in the adult mouse striatum

Striatal projection neurons (SPNs) are traditionally segregated into two subpopulations expressing dopamine (DA) D1-like or D2-like receptors. However, this dichotomy is challenged by recent evidence. Functional and expression studies raise important questions: do SPNs co-express different DA receptors, and do these differences reflect unique striatal spatial distributions and expression profiles? Using RNAscope in mouse striatum, we report heterogenous SPN subpopulations distributed across dorsal-ventral and rostral-caudal axes. SPN subpopulations co-express multiple DA receptors, including D1 and D2 (D1/2R) and D1 and D3. Our integrative approach using single-nuclei multi-omics analyses provides a simple consensus to describe SPNs across diverse datasets, connecting it to complementary spatial mapping. Combining RNAscope and multi-omics shows D1/2R SPNs further separate into distinct subtypes according to spatial organization and conserved marker genes. Each SPN cell type contributes uniquely to genetic risk for neuropsychiatric diseases. Our results bridge anatomy and transcriptomics to offer new understandings of striatal neuron heterogeneity.

neuroscience↗

bioRxiv2022

A spatial atlas of Wnt and Frizzled receptor expression in adult mouse liver

Hepatic zonation is critical for most metabolic functions in liver. Wnt signaling plays an important role in establishing and maintaining liver zonation. Yet, the anatomic expression of Wnt signaling components, including all 10 Frizzled receptors (Fzds), has not been characterized in adult liver. To address this, we quantitatively mapped the spatial expression of Wnt/Fzd pathway components in adult mouse liver via multiplex fluorescent in situ hybridization. While all 10 Fzds are expressed within a metabolic unit, Fzds 1, 4, and 6 are the highest expressed. Though the majority of Wnt signaling occurs in zone 3, expression of most Fzds is not zonated. In contrast, Fzd6 is preferentially expressed in zone 1. We also discovered that Wnt2 and Wnt9b expression is highly zonated and primarily found in zone 3. Therefore, our results suggest that zonated Wnt expression is critical for zonation maintenance in healthy adult liver. Finally, we showed that Fzds and Wnts are not uniformly expressed by all hepatic cell types. Rather, there is broad distribution among both hepatocytes and non-parenchymal cells, including endothelial cells. Overall, our establishment of a definitive mRNA expression atlas of Wnt/Fzd pathway components opens the door to future functional characterization in healthy and disease states.

cell biology↗