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Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility
Although autism is typically characterized by differences in language, social interaction and restrictive, repetitive behaviors, it is becoming more well known in the field that alterations in energy metabolism and mitochondrial function are comorbid disorders in autism. The synaptic cell adhesion m...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558836/ https://www.ncbi.nlm.nih.gov/pubmed/35617143 http://dx.doi.org/10.1093/hmg/ddac115 |
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author | Levy, Kyra A Weisz, Eliana D Jongens, Thomas A |
author_facet | Levy, Kyra A Weisz, Eliana D Jongens, Thomas A |
author_sort | Levy, Kyra A |
collection | PubMed |
description | Although autism is typically characterized by differences in language, social interaction and restrictive, repetitive behaviors, it is becoming more well known in the field that alterations in energy metabolism and mitochondrial function are comorbid disorders in autism. The synaptic cell adhesion molecule, neurexin-1 (NRXN1), has previously been implicated in autism, and here we show that in Drosophila melanogaster, the homologue of NRXN1, called Nrx-1, regulates energy metabolism and nutrient homeostasis. First, we show that Nrx-1-null flies exhibit decreased resistance to nutrient deprivation and heat stress compared to controls. Additionally, Nrx-1 mutants exhibit a significantly altered metabolic profile characterized by decreased lipid and carbohydrate stores. Nrx-1-null Drosophila also exhibit diminished levels of nicotinamide adenine dinucleotide (NAD(+)), an important coenzyme in major energy metabolism pathways. Moreover, loss of Nrx-1 resulted in striking abnormalities in mitochondrial morphology in the flight muscle of Nrx-1-null Drosophila and impaired flight ability in these flies. Further, following a mechanical shock Nrx-1-null flies exhibited seizure-like activity, a phenotype previously linked to defects in mitochondrial metabolism and a common symptom of patients with NRXN1 deletions. The current studies indicate a novel role for NRXN1 in the regulation of energy metabolism and uncover a clinically relevant seizure phenotype in Drosophila lacking Nrx-1. |
format | Online Article Text |
id | pubmed-9558836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95588362022-10-18 Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility Levy, Kyra A Weisz, Eliana D Jongens, Thomas A Hum Mol Genet Original Article Although autism is typically characterized by differences in language, social interaction and restrictive, repetitive behaviors, it is becoming more well known in the field that alterations in energy metabolism and mitochondrial function are comorbid disorders in autism. The synaptic cell adhesion molecule, neurexin-1 (NRXN1), has previously been implicated in autism, and here we show that in Drosophila melanogaster, the homologue of NRXN1, called Nrx-1, regulates energy metabolism and nutrient homeostasis. First, we show that Nrx-1-null flies exhibit decreased resistance to nutrient deprivation and heat stress compared to controls. Additionally, Nrx-1 mutants exhibit a significantly altered metabolic profile characterized by decreased lipid and carbohydrate stores. Nrx-1-null Drosophila also exhibit diminished levels of nicotinamide adenine dinucleotide (NAD(+)), an important coenzyme in major energy metabolism pathways. Moreover, loss of Nrx-1 resulted in striking abnormalities in mitochondrial morphology in the flight muscle of Nrx-1-null Drosophila and impaired flight ability in these flies. Further, following a mechanical shock Nrx-1-null flies exhibited seizure-like activity, a phenotype previously linked to defects in mitochondrial metabolism and a common symptom of patients with NRXN1 deletions. The current studies indicate a novel role for NRXN1 in the regulation of energy metabolism and uncover a clinically relevant seizure phenotype in Drosophila lacking Nrx-1. Oxford University Press 2022-05-25 /pmc/articles/PMC9558836/ /pubmed/35617143 http://dx.doi.org/10.1093/hmg/ddac115 Text en © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Levy, Kyra A Weisz, Eliana D Jongens, Thomas A Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
title | Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
title_full | Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
title_fullStr | Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
title_full_unstemmed | Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
title_short | Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
title_sort | loss of neurexin-1 in drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558836/ https://www.ncbi.nlm.nih.gov/pubmed/35617143 http://dx.doi.org/10.1093/hmg/ddac115 |
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