Browsing by Subject "neurodevelopment"

Now showing 1 - 4 of 4
  • Thumbnail Image
    ItemOpen Access
    Annual Research Review: Prenatal opioid exposure - a two-generation approach to conceptualizing neurodevelopmental outcomes.
    (Journal of child psychology and psychiatry, and allied disciplines, 2023-02) Conradt, Elisabeth; Camerota, Marie; Maylott, Sarah; Lester, Barry M
    Opioid use during pregnancy impacts the health and well-being of two generations: the pregnant person and the child. The factors that increase risk for opioid use in the adult, as well as those that perpetuate risk for the caregiver and child, oftentimes replicate across generations and may be more likely to affect child neurodevelopment than the opioid exposure itself. In this article, we review the prenatal opioid exposure literature with the perspective that this is not a singular event but an intergenerational cascade of events. We highlight several mechanisms of transmission across generations: biological factors, including genetics and epigenetics and the gut-brain axis; parent-child mechanisms, such as prepregnancy experience of child maltreatment, quality of parenting, infant behaviors, neonatal opioid withdrawal diagnosis, and broader environmental contributors including poverty, violence exposure, stigma, and Child Protective Services involvement. We conclude by describing ways in which intergenerational transmission can be disrupted by early intervention.
  • Thumbnail Image
    ItemOpen Access
    Cumulative stress in childhood is associated with blunted reward-related brain activity in adulthood.
    (Soc Cogn Affect Neurosci, 2016-03) Hanson, JL; Albert, WD; Iselin, AR; Carré, JM; Dodge, KA; Hariri, AR
    Early life stress (ELS) is strongly associated with negative outcomes in adulthood, including reduced motivation and increased negative mood. The mechanisms mediating these relations, however, are poorly understood. We examined the relation between exposure to ELS and reward-related brain activity, which is known to predict motivation and mood, at age 26, in a sample followed since kindergarten with annual assessments. Using functional neuroimaging, we assayed individual differences in the activity of the ventral striatum (VS) during the processing of monetary rewards associated with a simple card-guessing task, in a sample of 72 male participants. We examined associations between a cumulative measure of ELS exposure and VS activity in adulthood. We found that greater levels of cumulative stress during childhood and adolescence predicted lower reward-related VS activity in adulthood. Extending this general developmental pattern, we found that exposure to stress early in development (between kindergarten and grade 3) was significantly associated with variability in adult VS activity. Our results provide an important demonstration that cumulative life stress, especially during this childhood period, is associated with blunted reward-related VS activity in adulthood. These differences suggest neurobiological pathways through which a history of ELS may contribute to reduced motivation and increased negative mood.
  • Thumbnail Image
    ItemOpen Access
    Exploring the brain epitranscriptome: perspectives from the NSAS summit.
    (Frontiers in neuroscience, 2023-01) Lee, Sung-Min; Koo, Bonsang; Carré, Clément; Fischer, André; He, Chuan; Kumar, Ajeet; Liu, Kathy; Meyer, Kate D; Ming, Guo-Li; Peng, Junmin; Roignant, Jean-Yves; Storkebaum, Erik; Sun, Shuying; De Pietri Tonelli, Davide; Wang, Yinsheng; Weng, Yi-Lan; Pulvirenti, Luigi; Shi, Yanhong; Yoon, Ki-Jun; Song, Hongjun
    Increasing evidence reinforces the essential function of RNA modifications in development and diseases, especially in the nervous system. RNA modifications impact various processes in the brain, including neurodevelopment, neurogenesis, neuroplasticity, learning and memory, neural regeneration, neurodegeneration, and brain tumorigenesis, leading to the emergence of a new field termed neuroepitranscriptomics. Deficiency in machineries modulating RNA modifications has been implicated in a range of brain disorders from microcephaly, intellectual disability, seizures, and psychiatric disorders to brain cancers such as glioblastoma. The inaugural NSAS Challenge Workshop on Brain Epitranscriptomics hosted in Crans-Montana, Switzerland in 2023 assembled a group of experts from the field, to discuss the current state of the field and provide novel translational perspectives. A summary of the discussions at the workshop is presented here to simulate broader engagement from the general neuroscience field.
  • Thumbnail Image
    ItemOpen Access
    The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription.
    (The Journal of biological chemistry, 2020-05-11) Chen, Liang-Fu; Lyons, Michelle R; Liu, Fang; Green, Matthew V; Hedrick, Nathan G; Williams, Ashley B; Narayanan, Arthy; Yasuda, Ryohei; West, Anne E
    N-methyl-D-aspartate type glutamate receptors (NMDARs) are key mediators of synaptic activity-regulated gene transcription in neurons, both during development and in the adult brain. Developmental differences in the glutamate receptor ionotropic NMDA 2 (GluN2) subunit composition of NMDARs determines whether they activate the transcription factor cAMP-responsive element-binding protein 1 (CREB). However, whether the developmentally regulated GluN3A subunit also modulates NMDAR-induced transcription is unknown. Here, using an array of techniques, including quantitative real-time PCR, immunostaining, reporter gene assays, RNA sequencing, and two-photon glutamate uncaging with calcium imaging, we show that knocking down GluN3A in rat hippocampal neurons promotes the inducible transcription of a subset of NMDAR-sensitive genes. We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein (MAP) kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity-induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). Our evidence that GluN3A regulates MEF2C-dependent transcription reveals a novel mechanism by which NMDAR subunit composition confers specificity to the program of synaptic activity-regulated gene transcription in developing neurons.