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Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome,...

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Autores principales: Alamilla, Javier, Ramiro-Cortés, Yazmín, Mejía-López, Adriana, Chavez, José-Luis, Rivera, Dulce Olivia, Felipe, Víctor, Aguilar-Roblero, Raúl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930753/
https://www.ncbi.nlm.nih.gov/pubmed/33679297
http://dx.doi.org/10.3389/fnins.2021.604165
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author Alamilla, Javier
Ramiro-Cortés, Yazmín
Mejía-López, Adriana
Chavez, José-Luis
Rivera, Dulce Olivia
Felipe, Víctor
Aguilar-Roblero, Raúl
author_facet Alamilla, Javier
Ramiro-Cortés, Yazmín
Mejía-López, Adriana
Chavez, José-Luis
Rivera, Dulce Olivia
Felipe, Víctor
Aguilar-Roblero, Raúl
author_sort Alamilla, Javier
collection PubMed
description Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3(+/–) mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3(+/–) mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light–dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3(+/–) mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3(+/–) animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3(+/–) mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons.
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spelling pubmed-79307532021-03-05 Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse Alamilla, Javier Ramiro-Cortés, Yazmín Mejía-López, Adriana Chavez, José-Luis Rivera, Dulce Olivia Felipe, Víctor Aguilar-Roblero, Raúl Front Neurosci Neuroscience Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3(+/–) mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3(+/–) mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light–dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3(+/–) mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3(+/–) animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3(+/–) mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons. Frontiers Media S.A. 2021-02-18 /pmc/articles/PMC7930753/ /pubmed/33679297 http://dx.doi.org/10.3389/fnins.2021.604165 Text en Copyright © 2021 Alamilla, Ramiro-Cortés, Mejía-López, Chavez, Rivera, Felipe and Aguilar-Roblero. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Alamilla, Javier
Ramiro-Cortés, Yazmín
Mejía-López, Adriana
Chavez, José-Luis
Rivera, Dulce Olivia
Felipe, Víctor
Aguilar-Roblero, Raúl
Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse
title Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse
title_full Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse
title_fullStr Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse
title_full_unstemmed Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse
title_short Altered Light Sensitivity of Circadian Clock in Shank3(+/–) Mouse
title_sort altered light sensitivity of circadian clock in shank3(+/–) mouse
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930753/
https://www.ncbi.nlm.nih.gov/pubmed/33679297
http://dx.doi.org/10.3389/fnins.2021.604165
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