Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption.

Hunger and thirst have distinct goals but control similar ingestive behaviors, and little is known about neural processes that are shared between these behavioral states. We identify glutamatergic neurons in the peri-locus coeruleus (periLCVGLUT2 neurons) as a polysynaptic convergence node from separate energy-sensitive and hydration-sensitive cell populations. We develop methods for stable hindbrain calcium imaging in free-moving mice, which show that periLCVGLUT2 neurons are tuned to ingestive behaviors and respond similarly to food or water consumption. PeriLCVGLUT2 neurons are scalably inhibited by palatability and homeostatic need during consumption. Inhibition of periLCVGLUT2 neurons is rewarding and increases consumption by enhancing palatability and prolonging ingestion duration. These properties comprise a double-negative feedback relationship that sustains food or water consumption without affecting food- or water-seeking. PeriLCVGLUT2 neurons are a hub between hunger and thirst that specifically controls motivation for food and water ingestion, which is a factor that contributes to hedonic overeating and obesity.

Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition.

The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.

Combined Experiments with in Vivo Fiber Photometry and Behavior Tests Can Facilitate the Measurement of Neuronal Activity in the Primary Somatosensory Cortex and Hyperalgesia in an Inflammatory Pain Mice Model.

The pain matrix, which includes several brain regions that respond to pain sensation, contribute to the development of chronic pain. Thus, it is essential to understand the mechanism of causing chronic pain in the pain matrix such as anterior cingulate (ACC), or primary somatosensory (S1) cortex. Recently, combined experiment with the behavior tests and in vivo calcium imaging using fiber photometry revealed the interaction between the neuronal function in deep brain regions of the pain matrix including ACC and the phenotype of chronic pain. However, it remains unclear whether this combined experiment can identify the interaction between neuronal activity in S1, which receive pain sensation, and pain behaviors such as hyperalgesia or allodynia. In this study, to examine whether the interaction between change of neuronal activity in S1 and hyperalgesia in hind paw before and after causing inflammatory pain was detected from same animal, the combined experiment of in vivo fiber photometry system and von Frey hairs test was applied. This combined experiment detected that amplitude of calcium responses in S1 neurons increased and the mechanical threshold of hind paw decreased from same animals which have an inflammatory pain. Moreover, we found that the values between amplitude of calcium responses and mechanical thresholds were shifted to negative correlation after causing inflammatory pain. Thus, the combined experiment with fiber photometry and the behavior tests has a possibility that can simultaneously consider the interaction between neuronal activity in pain matrix and pain induced behaviors and the effects of analgesics or pain treatments.

Volatile Organic Compounds from Offspring of Stingless Bee Sacrificed in Hygienic Behavior Test.

This study shows the profile of volatile organic compounds (VOCs) from pupae and larvae of Melipona quadrifasciata anthidioides Lepeletier subjected to three death induction techniques for hygienic behavior (HB) studies: freezing in liquid nitrogen (LN2), freezing in a freezer (FRZ) and piercing of offspring with an entomological pin (PIN). The VOCs from larvae and pupae were obtained through headspace solid-phase microextraction and characterized using gas chromatography coupled to mass spectrometry. In addition, an HB test was performed on the colonies. The main classes of VOCs were hydrocarbons, terpenes and alcohols. Multivariate analysis was applied and showed that there was a separation in the compound profiles between the different treatments. The HB test in the colonies showed that 24 hours after the application of the techniques, the bees removed more dead larvae in LN2 treatment (83.5 %), while after 48 hours more larvae were removed in the LN2 and FRZ treatments (92.3 %). When compared to pupae removal, larvae removal was significantly faster in LN2.

Tailored behavioural tests reveal early and progressive cognitive deficits in M1000 prion disease.

Prion diseases are pathogenically linked to the normal cellular prion protein (PrPC) misfolding into abnormal conformers (PrPSc), with PrPSc accumulation underpinning both transmission and neurotoxicity. Despite achieving this canonical understanding, however fundamental questions remain incompletely resolved, including the level of pathophysiological overlap between neurotoxic and transmitting species of PrPSc and the temporal profiles of their propagation. To further investigate the likely time of occurrence of significant levels of neurotoxic species during prion disease development, the well characterised in vivo M1000 murine model was employed. Following intracerebral inoculation, detailed serial cognitive and ethological testing at specified time points suggested subtle transition to early symptomatic disease from ∼50% of the overall disease course. In addition to observing a chronological order for impaired behaviours, different behavioural tests also showed distinctive profiles of evolving cognitive impairments with the Barnes maze demonstrating a relatively simple linear worsening of spatial learning and memory over an extended period while in contrast a conditioned fear memory paradigm previously untested in murine prion disease demonstrated more complex alterations during disease progression. These observations support the likely production of neurotoxic PrPSc from at least just prior to the mid-point of murine M1000 prion disease and illustrate the likely need to tailor the types of behavioural testing across the time course of disease progression for optimal detection of cognitive deficits.

How Does Self-Control Promote Health Behaviors? A Multi-Behavior Test of Five Potential Pathways.

BACKGROUND: Self-control is generally defined as the capacity to override impulses and is a robust predictor of health behaviors. This paper integrates trait, reasoned action, and habit approaches to develop and test a mechanistic account of how self-control influences health actions. PURPOSE: We tested five potential pathways from self-control to behavior, termed the valuation, prioritization, habituation, translation, and inhibition routes. METHODS: At baseline, participants (N = 663 adults) completed survey measures of reasoned action approach variables and habits in relation to eight health behaviors and the Brief Self-Control Scale. Three months later, participants reported their behavior. Multi-level modeling was used to test pathways across behaviors. RESULTS: Supporting the valuation route, affective attitude, cognitive attitude, descriptive norms, and perceived behavioral control mediated the self-control-intention relation, and intentions and perceived behavioral control mediated the relationship between self-control and health behaviors. Self-control also predicted the priority accorded to different considerations during intention formation. Higher self-control was associated with stronger prediction by cognitive attitudes and perceived behavioral control and weaker prediction by habits and injunctive norms. Self-control predicted habit formation, and habits mediated the self-control-behavior relation. Finally, self-control was associated with the improved translation of intentions into health behaviors and with greater inhibition of affective and habitual influences. Findings for the different pathways were not moderated by whether approach (health-protective behaviors) or avoidance responses (health-risk behaviors) were at issue. CONCLUSIONS: The present research offers new insights into why self-control promotes health behavior performance, and how deficits in self-control might be offset in future behavior-change interventions.

Self-control is the capacity to override impulses and is known to predict engagement in health behaviors. This article tests five hypotheses about how self-control drives health actions. We find that high self-control not only helps to override impulses (feelings and habits), it also influences (a) how favorable are people's thoughts, feelings, and intentions about health behaviors, (b) what considerations determine the intention to act (e.g., high self-control means people give higher priority to the perceived healthiness of the behavior and how much control they have over its performance), (c) whether people form habits that make it less effortful to perform health behaviors, and (d) how effectively people translate their "good" intentions into health behaviors. Thus, we find support for five different routes from self-control to engagement in health behaviors.

Time cells in the human hippocampus and entorhinal cortex support episodic memory.

The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of "time cells" in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories.

The frequency of cortical microstimulation shapes artificial touch.

Intracortical microstimulation (ICMS) of the somatosensory cortex evokes vivid tactile sensations and can be used to convey sensory feedback from brain-controlled bionic hands. Changes in ICMS frequency lead to changes in the resulting sensation, but the discriminability of frequency has only been investigated over a narrow range of low frequencies. Furthermore, the sensory correlates of changes in ICMS frequency remain poorly understood. Specifically, it remains to be elucidated whether changes in frequency only modulate sensation magnitude-as do changes in amplitude-or whether they also modulate the quality of the sensation. To fill these gaps, we trained monkeys to discriminate the frequency of ICMS pulse trains over a wide range of frequencies (from 10 to 400 Hz). ICMS amplitude also varied across stimuli to dissociate sensation magnitude from ICMS frequency and ensure that animals could not make frequency judgments based on magnitude. We found that animals could consistently discriminate ICMS frequency up to ∼200 Hz but that the sensory correlates of frequency were highly electrode dependent: On some electrodes, changes in frequency were perceptually distinguishable from changes in amplitude-seemingly giving rise to a change in sensory quality; on others, they were not. We discuss the implications of our findings for neural coding and for brain-controlled bionic hands.

Molecular Landscape of Tourette's Disorder.

Tourette's disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. Yet, the molecular mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data to compile a list of TD candidate genes, and we subsequently conducted tissue/cell type specificity and functional enrichment analyses of this list. Using genomic data, we also investigated genetic sharing between TD and blood and cerebrospinal fluid (CSF) metabolite levels. Lastly, we built a molecular landscape of TD through integrating the results from these analyses with an extensive literature search to identify the interactions between the TD candidate genes/proteins and metabolites. We found evidence for an enriched expression of the TD candidate genes in four brain regions and the pituitary. The functional enrichment analyses implicated two pathways ('cAMP-mediated signaling' and 'Endocannabinoid Neuronal Synapse Pathway') and multiple biological functions related to brain development and synaptic transmission in TD etiology. Furthermore, we found genetic sharing between TD and the blood and CSF levels of 39 metabolites. The landscape of TD not only provides insights into the (altered) molecular processes that underlie the disease but, through the identification of potential drug targets (such as FLT3, NAALAD2, CX3CL1-CX3CR1, OPRM1, and HRH2), it also yields clues for developing novel TD treatments.

Effect Sizes of Cognitive and Locomotive Behavior Tests in the 5XFAD-J Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid ß (Aß) plaques in the brain, leading to cognitive impairment and other clinical symptoms. The 5XFAD mouse model is commonly used in AD research because it expresses five human transgenes that result in the accumulation of Aß plaques and cognitive decline at a relatively early age. Behavioral experiments are frequently conducted using this model; however, the effect size has not yet been reported. In this study, we examined basic cognition and locomotion in 5XFAD mice with a C57BL6/J background (5XFAD-J) at 6 months of age, a period in which impairments of cognitive function and locomotion are commonly observed. We analyzed the effect sizes of cognitive and locomotive experiments in the 5XFAD mice compared with those in the wild-type mice. Our results suggest that for long-term memory analysis, the novel object recognition test (p = 0.013, effect size 1.24) required a sample size of at least 12 to obtain meaningful results. Moreover, analysis of general locomotion over total distance with the Laboratory Animal Behavior Observation, Registration and Analysis System (LABORAS) test during the dark phase (p = 0.007, effect size -1.37) needed a sample size of 10 for a statistical power (1-ß) of 0.8. In conclusion, we can conduct more ethical and scientifically rigorous animal experiments using 5XFAD mice based on the effect and sample sizes suggested in this study.

Assessing the importance of sex in a hippocampus-dependent behavioral test battery in C57BL/6NTac mice.

Inclusion of male and female subjects in behavioral neuroscience research requires a concerted effort to characterize sex differences in standardized behavioral assays. Sex differences in hippocampus-dependent assays have been widely reported but are still poorly characterized. In the present study, we conducted a parametric analysis of spontaneous alternation, object recognition, and fear conditioning in a commonly used control strain, C57BL/6NTac. Our findings show largely similar performance between males and females across the majority of behavioral end points. However, we identified an important difference in nonassociative fear sensitization, whereby females showed an enhanced fear response to the 75-dB tone that is used as the conditional stimulus. In addition, we observed an impairment in object location performance in females that was ameliorated by more extensive habituation to handling. Together, these findings argue that sex differences in nonassociative fear responses to both novel auditory cues and novel objects need to be considered when designing and interpreting cognitive assays in C57BL/6 mice. Furthermore, this elevated fear sensitization could serve as a novel approach to model the increased incidence of anxiety disorders in women.

Application of Behavioral Tests for Evaluation of an Experimental Model of Alzheimer's Disease in Female Rats.

Alzheimer's disease was modeled in female Wistar rats aged 4 months by stereotaxic bilateral injection of a synthetic peptide ß-amyloid (Aß1-42) into the hippocampus. Behavioral tests (open field, Y-maze, passive avoidance, and Morris water maze) revealed significant impairment of memory and spatial navigation 8 weeks after ß-amyloid administration. At this term, the cognitive impairments typical of Alzheimer's disease are reproduced. The experimental model of Alzheimer's disease proposed by us can be used in preclinical studies of drugs for the treatment of this pathology.

Treatment with JQ1, a BET bromodomain inhibitor, is selectively detrimental to R6/2 Huntington's disease mice.

Transcriptional and epigenetic alterations occur early in Huntington's disease (HD), and treatment with epigenetic modulators is beneficial in several HD animal models. The drug JQ1, which inhibits histone acetyl-lysine reader bromodomains, has shown promise for multiple cancers and neurodegenerative disease. We tested whether JQ1 could improve behavioral phenotypes in the R6/2 mouse model of HD and modulate HD-associated changes in transcription and epigenomics. R6/2 and non-transgenic (NT) mice were treated with JQ1 daily from 5 to 11 weeks of age and behavioral phenotypes evaluated over this period. Following the trial, cortex and striatum were isolated and subjected to mRNA-seq and ChIP-seq for the histone marks H3K4me3 and H3K27ac. Initially, JQ1 enhanced motor performance in NT mice. In R6/2 mice, however, JQ1 had no effect on rotarod or grip strength but exacerbated weight loss and worsened performance on the pole test. JQ1-induced gene expression changes in NT mice were distinct from those in R6/2 and primarily involved protein translation and bioenergetics pathways. Dysregulation of HD-related pathways in striatum was exacerbated by JQ1 in R6/2 mice, but not in NTs, and JQ1 caused a corresponding increase in the formation of a mutant huntingtin protein-dependent high molecular weight species associated with pathogenesis. This study suggests that drugs predicted to be beneficial based on their mode of action and effects in wild-type or in other neurodegenerative disease models may have an altered impact in the HD context. These observations have important implications in the development of epigenetic modulators as therapies for HD.

Brain Proteome and Behavioural Analysis in Wild Type, BDNF+/- and BDNF-/- Adult Zebrafish (Danio rerio) Exposed to Two Different Temperatures.

Experimental evidence suggests that environmental stress conditions can alter the expression of BDNF and that the expression of this neurotrophin influences behavioural responses in mammalian models. It has been recently demonstrated that exposure to 34 °C for 21 days alters the brain proteome and behaviour in zebrafish. The aim of this work was to investigate the role of BDNF in the nervous system of adult zebrafish under control and heat treatment conditions. For this purpose, zebrafish from three different genotypes (wild type, heterozygous BDNF+/- and knock out BDNF-/-) were kept for 21 days at 26 °C or 34 °C and then euthanized for brain molecular analyses or subjected to behavioural tests (Y-maze test, novel tank test, light and dark test, social preference test, mirror biting test) for assessing behavioural aspects such as boldness, anxiety, social preference, aggressive behaviour, interest for the novel environment and exploration. qRT-PCR analysis showed the reduction of gene expression of BDNF and its receptors after heat treatment in wild type zebrafish. Moreover, proteomic analysis and behavioural tests showed genotype- and temperature-dependent effects on brain proteome and behavioural responding. Overall, the absent expression of BDNF in KO alters (1) the brain proteome by reducing the expression of proteins involved in synapse functioning and neurotransmitter-mediated transduction; (2) the behaviour, which can be interpreted as bolder and less anxious and (3) the cellular and behavioural response to thermal treatment.

Slingshot Challenge and Star Mines: Two digital games as a prisoner's dilemma to assess cooperation in children.

The prisoner's dilemma (PD) has been widely adopted by researchers to investigate cooperation among adults and children. However, studies using the PD with children are not as extensive as experiments with adults. The main aim of this work was to introduce and show the feasibility and validity of two digital games with the structural features of a PD (Slingshot Challenge [SC] and Star Mines [SM]) to investigate children's cooperative behavior. In two experiments, 162 children aged 6 to 12 years played SC and SM in different conditions. It was observed that children understood the dynamics of a PD, and were highly motivated to play SC and SM. We found that participants were more cooperative playing SM than SC and cooperated conditionally as well. We also found that sex and first-trial cooperation were associated with higher levels of cooperation. The results support the utility of SC and SM as feasible, reliable, and valid instruments for assessing cooperative behavior in childhood.

Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model.

BACKGROUND: Germinal matrix hemorrhage (GMH) is defined by the rupture of immature blood vessels in the germinal matrix, where subsequent hemorrhage enters the subependymal zone and the cerebral lateral ventricles. The consequent blood clot has been identified as the causative factor of secondary brain injury, which triggers a series of complex parallel and sequential harmful mechanisms, including neuroinflammation. The orphan G-protein-coupled receptor 40 (GPR40), a free fatty acid (FFA) receptor 1, has been shown to exert anti-inflammatory effects when activated and improved outcomes in animal models of stroke. We aimed to investigate the anti-inflammatory effects of GPR40 and its underlying mechanisms after GMH. METHODS: GMH model was induced in 7-day-old rat pups by an intraparenchymal injection of bacterial collagenase. GPR40 agonist, GW9508, was administered intranasally 1 h, 25 h, and 49 h after GMH induction. CRISPR targeting GPR40, PAK4, and KDM6B were administered through intracerebroventricular injection 48 h before GMH induction. Neurologic scores, microglia polarization, and brain morphology were evaluated by negative geotaxis, right reflex, rotarod test, foot fault test, Morris water maze, immunofluorescence staining, Western blots, and nissl staining respectfully. RESULTS: The results demonstrated that GW9508 improved neurological and morphological outcomes after GMH in the short (24 h, 48 h, 72h) and long-term (days 21-27). However, the neuroprotective effects of treatment were abolished by GW1100, a selective GPR40 antagonist. GW9508 treatment increased populations of M2 microglia and decreased M1 microglia in periventricular areas 24 h after GMH induction. GW9508 upregulated the phosphorylation of PAK4, CREB, and protein level of KDM6B, CD206, IL-10, which was also met with the downregulation of inflammatory markers IL-1ß and TNF-α. The mechanism study demonstrated that the knockdown of GPR40, PAK4, and KDM6B reversed the neuroprotective effects brought on by GW9508. This evidence suggests that GPR40/PAK4/CREB/KDM6B signaling pathway in microglia plays a role in the attenuation of neuroinflammation after GMH. CONCLUSIONS: In conclusion, the present study demonstrates that the activation of GPR40 attenuated GMH-induced neuroinflammation through the activation of the PAK4/CREB/KDM6B signaling pathway, and M2 microglia may be a major mediator of this effect. Thus, GPR40 may serve as a potential target in the reduction of the inflammatory response following GMH, thereby improving neurological outcomes in the short- and long-term.

Validity and Reliability of Executive Function Measures in Children With Heavy Prenatal Alcohol Exposure: Correspondence Between Multiple Raters and Laboratory Measures.

BACKGROUND: Rating scales are designed to complement traditional performance-based measures, and both can provide useful information about the functioning of youth with histories of prenatal alcohol exposure. Few studies, however, have compared ratings from multiple informants or the relationship between these subjective rating scale scores and the objective results from laboratory performance-based scales. METHODS: The current study addressed both of these questions in 3 study groups: children with histories of prenatal alcohol exposure (n = 47), attention-deficit/hyperactivity disorder (ADHD; n = 41), and typically developing controls (CON; n = 73). All subjects completed a standardized neuropsychological test battery, including laboratory measures of executive functioning and a self-report measure of executive function behaviors. Parents and teachers completed corresponding rating scales of executive function behaviors for each subject. This study assessed the relationship between these behavior rating scales and corresponding neuropsychological tests, and interrater agreement among the multiple informants. RESULTS: Weak correlations were found between the rating scales and laboratory measures, indicating poor convergent validity for the behavior rating scale. Interrater reliability was found but it differed by group. Agreement was found between parent and teacher ratings for children with prenatal alcohol exposure, whereas teacher-child agreement was found for those with ADHD. CONCLUSIONS: Findings from this study indicate that behavior ratings can be used to supplement laboratory measures but may not be measuring cognitive abilities regardless of whether a clinical diagnosis is present. A multimethod approach should be used when measuring skills in this domain. This was one of the first studies to examine cross-informant agreement in a sample of children with prenatal alcohol exposure. Further research is necessary to understand why interrater agreement differed for children with prenatal alcohol exposure and those with ADHD.

Qualitative evaluation of the Autism Behavior Inventory: use of cognitive interviewing to establish validity of a caregiver report scale for autism spectrum disorder.

PURPOSE: The Autism Behavior Inventory (ABI) is an observer-reported outcome scale measuring core and associated features of autism spectrum disorder (ASD). Extensive scale development (reported elsewhere) took place, in alignment with the Food and Drug Administration's patient-reported outcome guidance, to address the need for instruments to measure change and severity of ASD symptoms. METHODS: Cognitive interviewing was used to confirm understanding and content validity of the scale prior to its use in clinical trials. Respondents were caregivers of individuals with ASD (N = 50). Interviews used a hybrid of the "think-aloud" and verbal probing approach to assess ABI's content validity and participant understanding of the instrument, including: item clarity and relevance; item interpretation; appropriateness of response scales; and clarity of instructions. Audio-recordings of the interviews were transcribed for qualitative data analysis. The scale was revised based on participant feedback and tested in a second round of interviews (round 1 N = 38, round 2 N = 12). RESULTS: In total, 67/70 items reached ≥ 90% understandability across participants. Caregivers were able to select an appropriate response from the options available and reported finding the examples helpful. Based on participant feedback, instructions were simplified, 8 items were removed, and 10 items were reworded. The final revised 62-item scale was presented in round 2, where caregivers reported readily understanding the instructions, response options, and 61/62 items reached ≥ 90% understandability. CONCLUSIONS: Cognitive interviews with caregivers of a diverse sample of individuals with ASD confirm the content validity and relevance of the ABI to assess core and associated symptoms of ASD.

Can Temperament and Character Traits Be Used in the Diagnostic Differentiation of Children With ADHD?

ABSTRACT: In this study, it was aimed to determine the contributions of temperament and character traits to the diagnosis of attention deficit hyperactivity disorder (ADHD) in children. Thirty-six patients between the ages of 9 and 14 with a diagnosis of combined type ADHD and 39 healthy children were included in the study. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version-Turkish Version and the Turgay DSM-IV Disruptive Behavior Disorders Rating Scale parent form were used to assess hyperactivity/impulsivity and inattentiveness, and comorbid disorders. The Junior Temperament and Character Inventory-Revised form was used to evaluate temperament-character traits. The classification-based association rules (CBARs) method was used for finding rules predicting ADHD accurately. Low persistence and self-directedness scores, and higher disorderliness and fatigability subgroup scores were found in the ADHD group. In CBARs, the separation of children with ADHD from healthy controls could be made with 0.83 accuracy, 0.80 sensitivity, and 0.86 specificity. The results of our study support the view that temperament-character traits can help clinical diagnosis of ADHD.

Integrating transcriptomics and behavior tests reveals how the C. elegans responds to copper induced aging.

Copper (Cu) pollution in water and agricultural soil has always been a worldwide concern. This research aims to investigate the health effects of copper exposure on Caenorhabditis elegans (C. elegans) under the existing environmental quality standards (1 mg/L and 2 mg/L) via lifespan, reproduction, biological markers and transcriptome analysis. The results showed that copper of these two environmental standards shorten the lifespan of nematodes, reduced the brood size, reduced the frequency of pharyngeal pumps and prolonged defecation time as aging-related behaviors, and increased the levels of aging-related markers ROS, MDA and H2O2. There was a certain effect trend for the two exposure concentrations. Further, the possible molecular mechanism of copper-induced aging and reproductive effects on C. elegans was explored. Differential gene expression analysis was performed, and 2332 genes (567 up- and 1765 down-regulated genes) in the 1 mg/L group, 2449 DEGs (724 up- and 1725 down-regulated genes) in the 2 mg/L group in response to copper treatment. The top 20 regulated genes were vit (vit-1, vit-3, vit-4) genes, col genes (col-35, col-72, col-114, col-123, col-164, col-183, col-185), eea-1, him-18 and grl-20, which suggested that cuticle collagen synthesis and yolk expression were disrupted by copper. Analysis of KEGG pathway showed copper exposure widely affects longevity regulation pathways, thereby promoting aging. In summary, the sequencing results extensively and deeply reveal the health hazards of environmentally relevant doses of copper exposure to C. elegans, and behavioral testing verified that copper promoted aging of C. elegans.