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Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder

Mutations in the TM4SF2 gene, which encodes TSPAN7, cause a severe form of intellectual disability (ID) often comorbid with autism spectrum disorder (ASD). Recently, we found that TM4SF2 loss in mice affects cognition. Here, we report that Tm4sf2(−/y) mice, beyond an ID-like phenotype, display alter...

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Autores principales: Murru, Luca, Ponzoni, Luisa, Longatti, Anna, Mazzoleni, Sara, Giansante, Giorgia, Bassani, Silvia, Sala, Mariaelvina, Passafaro, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840593/
https://www.ncbi.nlm.nih.gov/pubmed/33227491
http://dx.doi.org/10.1016/j.nbd.2020.105189
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author Murru, Luca
Ponzoni, Luisa
Longatti, Anna
Mazzoleni, Sara
Giansante, Giorgia
Bassani, Silvia
Sala, Mariaelvina
Passafaro, Maria
author_facet Murru, Luca
Ponzoni, Luisa
Longatti, Anna
Mazzoleni, Sara
Giansante, Giorgia
Bassani, Silvia
Sala, Mariaelvina
Passafaro, Maria
author_sort Murru, Luca
collection PubMed
description Mutations in the TM4SF2 gene, which encodes TSPAN7, cause a severe form of intellectual disability (ID) often comorbid with autism spectrum disorder (ASD). Recently, we found that TM4SF2 loss in mice affects cognition. Here, we report that Tm4sf2(−/y) mice, beyond an ID-like phenotype, display altered sociability, increased repetitive behaviors, anhedonic- and depressive-like states. Cognition relies on the integration of information from several brain areas. In this context, the lateral habenula (LHb) is strategically positioned to coordinate the brain regions involved in higher cognitive functions. Furthermore, in Tm4sf2(−/y) mice we found that LHb neurons present hypoexcitability, aberrant neuronal firing pattern and altered sodium and potassium voltage-gated ion channels function. Interestingly, we also found a reduced expression of voltage-gated sodium channel and a hyperactivity of the PKC-ERK pathway, a well-known modulator of ion channels activity, which might explain the functional phenotype showed by Tm4sf2(−/y) mice LHb neurons. These findings support Tm4sf2(−/y) mice as useful in modeling some ASD-like symptoms. Additionally, we can speculate that LHb functional alteration in Tm4sf2(−/y) mice might play a role in the disease pathophysiology.
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spelling pubmed-78405932021-02-01 Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder Murru, Luca Ponzoni, Luisa Longatti, Anna Mazzoleni, Sara Giansante, Giorgia Bassani, Silvia Sala, Mariaelvina Passafaro, Maria Neurobiol Dis Article Mutations in the TM4SF2 gene, which encodes TSPAN7, cause a severe form of intellectual disability (ID) often comorbid with autism spectrum disorder (ASD). Recently, we found that TM4SF2 loss in mice affects cognition. Here, we report that Tm4sf2(−/y) mice, beyond an ID-like phenotype, display altered sociability, increased repetitive behaviors, anhedonic- and depressive-like states. Cognition relies on the integration of information from several brain areas. In this context, the lateral habenula (LHb) is strategically positioned to coordinate the brain regions involved in higher cognitive functions. Furthermore, in Tm4sf2(−/y) mice we found that LHb neurons present hypoexcitability, aberrant neuronal firing pattern and altered sodium and potassium voltage-gated ion channels function. Interestingly, we also found a reduced expression of voltage-gated sodium channel and a hyperactivity of the PKC-ERK pathway, a well-known modulator of ion channels activity, which might explain the functional phenotype showed by Tm4sf2(−/y) mice LHb neurons. These findings support Tm4sf2(−/y) mice as useful in modeling some ASD-like symptoms. Additionally, we can speculate that LHb functional alteration in Tm4sf2(−/y) mice might play a role in the disease pathophysiology. Academic Press 2021-01 /pmc/articles/PMC7840593/ /pubmed/33227491 http://dx.doi.org/10.1016/j.nbd.2020.105189 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Murru, Luca
Ponzoni, Luisa
Longatti, Anna
Mazzoleni, Sara
Giansante, Giorgia
Bassani, Silvia
Sala, Mariaelvina
Passafaro, Maria
Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder
title Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder
title_full Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder
title_fullStr Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder
title_full_unstemmed Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder
title_short Lateral habenula dysfunctions in Tm4sf2(−/y) mice model for neurodevelopmental disorder
title_sort lateral habenula dysfunctions in tm4sf2(−/y) mice model for neurodevelopmental disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840593/
https://www.ncbi.nlm.nih.gov/pubmed/33227491
http://dx.doi.org/10.1016/j.nbd.2020.105189
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