Neurexins are neuronal adhesion molecules important for synapse maturation, function, and plasticity. Neurexins have been genetically associated with neurodevelopmental disorders including autism spectrum disorders (ASDs) and schizophrenia, but can have variable penetrance and phenotypic severity. Heritability studies indicate that a significant percentage of risk for ASD and schizophrenia includes environmental factors, highlighting the poorly understood interplay between genetic and environmental factors in pathogenesis of these disorders. The singular C. elegans ortholog of human neurexins, nrx-1, controls experience-dependent morphologic remodeling of a GABAergic neuron in adult males. Here I show that this GABAergic neuron's morphology is altered in response to each of three environmental stressors (nutritional, heat, or genotoxic stress) applied during sexual maturation, but not during adulthood. Increased outgrowth of axon-like neurites following adolescent stress results from an altered morphologic plasticity that occurs upon entry into adulthood. Despite axonal remodeling being induced by each of the three stressors, only nutritional stress (starvation) impacts behavior and is dependent on neurexin/nrx-1. Heat or genotoxic stress during sexual maturation did not alter behavior despite inducing GABAergic neuron remodeling, and this remodeling was independent of neurexin/nrx-1. Remodeling induced by starvation stress was found be dependent on neuroligin/nlg-1, the canonical binding partner for neurexin/nrx-1, as well as the stress signaling transcription factors FOXO/daf-16 and HSF1/hsf-1, each of which was also found to have unique roles in remodeling induced by heat and UV stress. The differential molecular mechanisms underlying GABAergic neuron remodeling in response to different stressors, and the disparate effects of stressors on behavior, is a novel paradigm for understanding how genetics, environmental exposures, and plasticity may contribute to brain dysfunction in ASDs and schizophrenia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.