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Caenorhabditis elegans neuroligin mutants, a model for Autism Spectrum Disorder associated behaviors

Undergraduate #139
Discipline: Neuroscience
Subcategory: Cell and Molecular Biology
Session: 4
Room: Exhibit Hall

Laura C. Benítez-Montalvo - Pontifical Catholic University of Puerto Rico – Ponce Campus
Co-Author(s): Darielys Maldonado, Pontifical Catholic University of Puerto Rico – Ponce Campus, Ponce, PR; Dinah L. Ramos-Ortolaza, Ph.D., Pontifical Catholic University of Puerto Rico – Ponce Campus, Ponce, PR



Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by challenges in social interactions, restrictive and repetitive behaviors, and strenuous non-verbal communication. The molecular mechanisms underlying ASD are unknown; however, mutations in the neuroligin gene have been linked to the development of this disorder. This gene codes for a protein involved in mechanisms that allow the cells to fight against oxidative stress. Mutations in this gene contribute to dysregulated levels of reactive oxygen species, consequently increasing oxidative stress, enabling cellular injury, inducing apoptosis, and disrupting intracellular signaling pathways. To this end, the nematode Caenorhabditis elegans is an excellent candidate to study the effects of oxidative stress in behavior because of its evolutionary conserved genes, which are homologous to humans. Therefore, we aimed to study how exposure to oxidative stress modifies sensory, motor, and social behavior in C. elegans neuroligin mutants. We hypothesized that neuroligin mutant strains, VC228, present decreased sensory responses, motor deficiencies, and diminished social behaviors compared to wild-type N2 nematodes. For this purpose, we cultivated the nematodes under oxidative stress conditions using 0.2mM paraquat and performed a series of behavioral assays: Chemotaxis, Thermotaxis, Aldicarb, and Starvation-Induced Behavior. Our results suggest that the C. elegans neuroligin mutants present substantial chemical and thermal perception deficiencies. Our results also indicate that the nematodes are more susceptible to aldicarb, a cholinesterase inhibitor widely used to study neuropeptide release at the neuromuscular junction. Ongoing experiments will provide insight into the social communication differences in the nematodes under oxidative stress, alongside the identification of the molecules through which oxidative stress and neuroligin contribute to such behavioral manifestations. Altogether, these findings demonstrate an association between the effects of oxidative stress on the behavioral manifestations that characterize ASD. Identifying the underlying cause of these behavioral mechanisms will provide a platform for further research and development of therapeutic strategies for ASD.

Funder Acknowledgement(s): 1. Padre Tosello Giangiacomo Scientific Research Center at the Pontifical Catholic University of Puerto Rico – Ponce Campus2. Puerto Rico Louis Stokes Alliance for Minority Participation (PR-LSAMP) Program (Award #1906130)

Faculty Advisor: Dinah L. Ramos-Ortolaza, Ph.D., dinah_ramos@pucpr.edu

Role: I actively participated in the cultivation and maintenance of the Caenorhabditis elegans strains, including preparation of media and their food source, Escherichia coli (OP50). Alongside this, I contributed to the preparation of materials within the methodology of this research and the execution of the technical-behavioral assays, focusing primarily on the Chemotaxis, Thermotaxis, Aldicarb, and Starvation-Induced Assays.

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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