Project description:We used Drosophila genetic and behavioral models to examine AMPH-induced transcriptional changes in DAT-dependent manner, as those would be the most relevant to the stimulatory effects of the drug in the brain. We previously showed that flies respond to AMPH by increasing their locomotor activity and decreasing their sleep in a dopamine-dependent manner. Flies that carry a loss-of-function mutation in the gene encoding the Drosophila DAT homolog (dDATfmn, henceforth referred to as DAT mutants) exhibit heightened activity levels at baseline, consistent with increased levels of extracellular dopamine caused by the impairment of reuptake. In this study we compared gene expression changes in response to AMPH in brains of isogenic w1118 strain (WT) and DAT mutants. We found genes involved in the control of mRNA translation to be significantly upregulated in response to AMPH in a DAT-dependent manner.
Project description:Domoic acid toxicosis (DAT) in California sea lions (Zalophus californianus) is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis in an effort to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. 49 spots were excised, digested and analyzed by MS/MS. These are the data.
Project description:Dopaminergic (DA) neurons marked by the dopamine transporter (DAT) have multiple physiological functions and are involved in the regulation of mental and neurological diseases, prompting in-depth studies into their development and functions. This research explores the spatiotemporal proteomic and transcriptomic changes in DAT+ DA neurons within key brain regions involved in DA signaling—the nucleus accumbens (NAc), substantia nigra (SNc), and ventral tegmental area (VTA). Utilizing cutting-edge multi-omics techniques, such as ultrasensitive trace sample proteomics and SMART_x0002_seq2 for transcriptomics, we examine the DA neuronal system at critical postnatal milestones: postnatal day 7 (P7), postnatal day 30 (P30), and postnatal day 60 (P60). The study reveals unique molecular profiles within DA neuron populations, showcasing their varied functional roles and developmental progression. Immunofluorescence mapping illustrates these molecular distributions, validating the quantitative data and highlighting the dynamic molecular structure of DA neurons. Our findings notably highlight a marked increase over time in Aldh1a1 expression, an essential enzyme for retinoic acid production, suggesting its evolving role in neuronal development and specific functions. This comprehensive analysis offers a profound molecular perspective on DAT+ DA neuron development, enhancing our understanding of their functional diversity and potential relevance in DA-related diseases.
