Transcriptomic profiles of consistent risk-taking behaviour across time and contexts in European sea bass
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ABSTRACT: Boldness is known to be a key driver of accessibility to food or reproduction, but also of increased risk including of being predated. Boldness is supposed consistent across time and contexts but studies investigating stability of this trait in variable environments, including in terms of stress load and over long periods of time are scarce. Moreover, underlying molecular components are poorly studied. Here, we report that boldness of 1154 European sea bass, evaluated using group risk-taking tests, is consistent over 7 months and for individuals subjected to multiple environments, including a stressful environment. Differences in risk-taking behaviour were strengthened by differences observed in the responses to a novel environment test; shy individuals displaed higher group dispersion, higher thigmotaxic behaviour and lower activity. Transcriptomic analyses performed on extreme phenotypes revealed that bold individuals display greater expression for genes involved in social and exploration behaviour, and memory in the pituitary, and genes involved in immunity and response to stimulus in the head kidney. This study demonstrates that personality traits come with underpinning molecular signature, especially in organs involved in the endocrine and immune systems. As such, our results may help to depict the state-behaviour feedback, previously proposed as key in shaping personality.
Project description:The Illumina Human Omni2.5 array is a high resolution microarray platform for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the risk factor CNVs in 281 individuals diagnosed with Antisocial Personality Disorder.
Project description:Drug addiction is a major public health issue that is characterised by continued drug use despite negative consequences. However, the molecular and cellular mechanisms that underlie this behaviour are not well understood. In this study we investigated the role of miR-137, a microRNA that has been previously shown to control the expression of genes necessary for neuronal development and synapse maturation, with common variants in the MIR137 gene linked to a higher risk of schizophrenia. Previously, we revealed that miR-137 expression in cocaine-trained animals exhibited spatial and temporal variability in the dorsal striatum (DS). Building upon this observation, we hypothesised that augmenting miR-137 function in the DS would impact drug-seeking behavior under punishment conditions by modulating molecular targets involved in synaptic plasticity. Male Sprague-Dawley rats were trained to self-administer cocaine and then randomly assigned to receive either lentiviral-mediated overexpression of hsa-miR-137 (miR-137OE) or an empty pCDH-vector (pCDH-EV) control in the dorsomedial striatum (DMS). Once stable cocaine self-administration was achieved, drug-taking was assessed under conditions in which lever presses were associated with a 0.25 probability of foot shock (0.5 mA). During five days of testing, pCDH-EV control animals showed a significant reduction in responding for cocaine, whereas miR-137OE animals displayed greater resistance to the suppression of cocaine responding across foot shock sessions compared to controls. RNA-sequencing analysis of striatal tissue from miR-137OE animals revealed significant enrichment of genes involved in synaptic plasticity and astrocyte signalling compared to control animals. Taken together, these findings provide insight into the mechanisms underlying addiction risk and and contribute to a better understanding of the neural substrates involved in these disorders.
Project description:Circadian rhythm disturbances have long been associated with the development of psychiatric disorders, including mood and substance use disorders. Adolescence is a particularly vulnerable time for the onset of psychiatric disorders and for circadian rhythm and sleep disruptions. Preclinical studies have found that circadian rhythm disruption (CRD) impacts the brain and behavior, but this research is largely focused on adult disruptions. Here, we sought to determine the long-term behavioral and neurobiological effects of CRD during early adolescence by exposing mice to 12 h shifts in the light/dark cycle. We hypothesized that adolescent CRD would have a greater effect on psychiatric-related behaviors, relative to adult disruption. To identify possible mechanisms, we also measured gene expression in brain regions relevant to circadian rhythms, mood and reward. We found that disruption during early adolescence, but not adulthood, persistently increased exploratory drive (risk-taking behavior) and cocaine preference when tested later in life. Interestingly, we found sex differences when intravenous cocaine self-administration was tested. While female mice with a history of adolescent CRD had a greater propensity to self-administer cocaine, as well as increased motivation and cue-induced reinstatement, male adolescent CRD mice had reduced motivation and extinction responding. Overall, adolescent CRD in mice caused persistent increases in risky behavior, cocaine reward and cocaine self-administration, which suggests that CRD during adolescence may predispose individuals towards substance use disorders. Importantly, we found that many transcripts were affected by adolescent CRD and these were largely distinct across sex and brain region. Future research is required to elucidate how adolescent CRD affects behaviors relevant to mood- and substance use-related disorders across the 24-hour day, as well as to identify intervention strategies to alleviate disruption during adolescence and novel therapeutic approaches once symptoms have begun.
Project description:Gene expression profiling was carried out on peripheral blood CD2+ leukocytes from 29 children with asthma. The primary research question is whether gene expression differs in individuals from high socioeconomic status environments vs low socioeconomic status environments. Keywords: Risk prediction
Project description:In previous studies, we employed multiple behavior assays, including propensity to feed, simulated trawl capture and escape response, to prove the presence of bold and shy personality in olive flounder. However, the molecular mechanism of the different personality has not been elucidated. In the present study, the transcriptomic profiles of the hindbrain from flounder with distinct personalities were compared. A total of 144 differently expressed genes were identified, including 74 up-regulated and 70 downregulated genes. Genes involved in hypoxia stress were detected in SP flounder, accompanied by down-regulation of ribosomal RNA synthesis. In addition, genes related to calcium signaling pathway, including endothelin, b-Fos, c-Fos and c-Jun were up-regulated in SP flounder. Furthermore, personality-related genes, including UI, CCK, c-Fos showed a significantly higher level in SP flounder compared with BP flounder. GO enrichment analysis indicated that the GO categories “the tight junction pathway” and “lipid transport or localization pathway” are enriched in SP flounder, suggesting that the central nervous system homeostasis would be compromised. Finally, a simple and scalable DNA methylation profiling allows for methylation analysis for different genes. The results found that part of gene expression is negatively related to methylation of promoter. Altogether, identification of the related genes in flounder with different personalities will shed new light to improve critical industry issues related to stress and increase aquaculture production of flounder.
Project description:Individual differences in basal leukocyte gene expression profiles as a function of Big 5 personality dimensions Gene expression profiling was carried out on peripheral blood mononuclear cell RNA samples collected from 119 healthy adults measured for the 5 major dimensions of human personality (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness) using the NEO-FFI 60-item personality inventory. Personality measures are z-score standardized. Analyses control for major demographic characteristics (age, sex, Caucasian vs Non-Caucasian race) as well as Body Mass Index (BMI), smoking (CigDay), alcohol consumption (AlcDay), and physical activity (ExerDay, hours per day). Additional secondary analyses controlled for the presence of minor physical symptoms (MinorSymptom, e.g.,hayfever, headache), medication use (BirthControl, Antidepressant, OtherMedication), and negative affective states (NegativeAffect, standardized values of PANAS Negative Affect scale). Experiment type: Risk prediction
Project description:Nicotine intake, whether through tobacco smoking or e-cigarettes, remains a global health concern. An emerging preclinical literature indicates that parental nicotine exposure produces behavioral, physiological, and molecular changes in subsequent generations. However, the heritable effects of voluntary parental nicotine taking are unknown. Here, we show increased acquisition of nicotine taking in male and female offspring of sires that self-administered nicotine. In contrast, self-administration of sucrose and cocaine were unaltered in male and female offspring suggesting that the intergenerational effects of paternal nicotine taking may be reinforcer specific. Further characterization revealed memory deficits and increased anxiety-like behaviors in drug-naïve male, but not female, offspring of nicotine-experienced sires. Using an unbiased, genome-wide approach, we discovered that these phenotypes were associated with decreased expression of Satb2, a transcription factor known to play important roles in synaptic plasticity and memory formation, in the hippocampus of nicotine-sired male offspring. This effect was sex-specific as no changes in Satb2 expression were found in nicotine-sired female offspring. Finally, increasing Satb2 levels in the hippocampus prevented the escalation of nicotine intake and rescued the memory deficits associated with paternal nicotine taking in male offspring. Collectively, these findings indicate that paternal nicotine taking produces heritable sex-specific molecular changes that promote addiction-like phenotypes and memory impairments in male offspring. To characterize the molecular changes associated with the heritable effects of paternal nicotine taking, an unbiased, whole-genome analysis was used to characterize the hippocampal transcriptome of drug-naïve F1 males