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Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal pathways of C. elegans.

Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal pathways of C. elegans.
Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal pathways of C. elegans.
Neuroligins are neuronal and neuromuscular transmembrane proteins that have been implicated in autism spectrum disorder and other cognitive diseases. The nlg-1 gene from Caenorhabditis elegans is orthologous to human neuroligin genes. In the nematode, the locomotory rate is mediated by dopaminergic and serotonergic pathways, which result in two different behavioral responses known as basal slowing response (BSR) and enhanced slowing response (ESR), respectively. We report that nlg-1-deficient mutants are defective in both the BSR and ESR behaviors. In addition, we demonstrate that methylphenidate (a dopamine reuptake inhibitor) and fluoxetine (a serotonin reuptake inhibitor), two drugs widely used for the treatment of behavioral disorders in humans, are able to restore the BSR and ESR wild type phenotypes, respectively, in nlg-1 defective mutant nematodes. The abnormal locomotory behavior patterns were rescued in nlg-1-deficient mutant by expressing a cDNA from the human NLGN1 gene under the C. elegans nlg-1 promoter. However, human NLGN1 (R453C) and NLGN1 (D432X) mutant alleles did not rescue any of the two mutant phenotypes. The results indicate that neuroligin is involved in modulating the action of dopamine and serotonin in the nematode and suggest that the functional mechanism underpinning both methylphenidate and fluoxetine in C. elegans might be comparable to that in humans. The neuroligin-deficient mutants may undergo inefficient synaptic transmissions which could affect different traits in the nervous system. In particular, neuroligin might be required for normal neurotransmitters release. The understanding of the mechanisms by which methylphenidate and fluoxetine are able to restore the behavior of these mutants could help to explain the etiology of some human neurological diseases.
1364-6745
233-42
Izquierdo, Patricia G.
819a11cd-238c-4031-901f-5921a04a20ee
Calahorro, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Ruiz-Rubio, Manuel
bb788f2e-5703-4b36-bd3e-1aa546997e61
Izquierdo, Patricia G.
819a11cd-238c-4031-901f-5921a04a20ee
Calahorro, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Ruiz-Rubio, Manuel
bb788f2e-5703-4b36-bd3e-1aa546997e61

Izquierdo, Patricia G., Calahorro, Fernando and Ruiz-Rubio, Manuel (2013) Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal pathways of C. elegans. Neurogenetics, 14 (3-4), 233-42. (doi:10.1007/s10048-013-0377-6). (PMID:24100941)

Record type: Article

Abstract

Neuroligins are neuronal and neuromuscular transmembrane proteins that have been implicated in autism spectrum disorder and other cognitive diseases. The nlg-1 gene from Caenorhabditis elegans is orthologous to human neuroligin genes. In the nematode, the locomotory rate is mediated by dopaminergic and serotonergic pathways, which result in two different behavioral responses known as basal slowing response (BSR) and enhanced slowing response (ESR), respectively. We report that nlg-1-deficient mutants are defective in both the BSR and ESR behaviors. In addition, we demonstrate that methylphenidate (a dopamine reuptake inhibitor) and fluoxetine (a serotonin reuptake inhibitor), two drugs widely used for the treatment of behavioral disorders in humans, are able to restore the BSR and ESR wild type phenotypes, respectively, in nlg-1 defective mutant nematodes. The abnormal locomotory behavior patterns were rescued in nlg-1-deficient mutant by expressing a cDNA from the human NLGN1 gene under the C. elegans nlg-1 promoter. However, human NLGN1 (R453C) and NLGN1 (D432X) mutant alleles did not rescue any of the two mutant phenotypes. The results indicate that neuroligin is involved in modulating the action of dopamine and serotonin in the nematode and suggest that the functional mechanism underpinning both methylphenidate and fluoxetine in C. elegans might be comparable to that in humans. The neuroligin-deficient mutants may undergo inefficient synaptic transmissions which could affect different traits in the nervous system. In particular, neuroligin might be required for normal neurotransmitters release. The understanding of the mechanisms by which methylphenidate and fluoxetine are able to restore the behavior of these mutants could help to explain the etiology of some human neurological diseases.

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Published date: November 2013
Organisations: Biomedicine

Identifiers

Local EPrints ID: 366691
URI: https://eprints.soton.ac.uk/id/eprint/366691
ISSN: 1364-6745
PURE UUID: a2c2c08e-6a9c-42d6-8776-6d17dd73a982
ORCID for Fernando Calahorro: ORCID iD orcid.org/0000-0003-0659-7728

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Date deposited: 07 Jul 2014 13:12
Last modified: 20 Jul 2019 00:39

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