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Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion
The mechanistic target of rapamycin (mTOR) pathway is a signaling system integral to neural growth and migration. In both patients and rodent models, mutations to the phosphatase and tensin homolog gene (PTEN) on chromosome 10 results in hyperactivation of the mTOR pathway, as well as seizures, inte...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393422/ https://www.ncbi.nlm.nih.gov/pubmed/37376966 http://dx.doi.org/10.1111/gbb.12854 |
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author | Narvaiz, David A. Nolan, Suzanne O. Smith, Gregory D. Holley, Andrew J. Reynolds, Conner D. Blandin, Katherine J. Nguyen, Phuoc H. Tran, Doan L. K. Lugo, Joaquin N. |
author_facet | Narvaiz, David A. Nolan, Suzanne O. Smith, Gregory D. Holley, Andrew J. Reynolds, Conner D. Blandin, Katherine J. Nguyen, Phuoc H. Tran, Doan L. K. Lugo, Joaquin N. |
author_sort | Narvaiz, David A. |
collection | PubMed |
description | The mechanistic target of rapamycin (mTOR) pathway is a signaling system integral to neural growth and migration. In both patients and rodent models, mutations to the phosphatase and tensin homolog gene (PTEN) on chromosome 10 results in hyperactivation of the mTOR pathway, as well as seizures, intellectual disabilities and autistic behaviors. Rapamycin, an inhibitor of mTOR, can reverse the epileptic phenotype of neural subset specific Pten knockout (NS‐Pten KO) mice, but its impact on behavior is not known. To determine the behavioral effects of rapamycin, male and female NS‐Pten KO and wildtype (WT) mice were assigned as controls or administered 10 mg/kg of rapamycin for 2 weeks followed by behavioral testing. Rapamycin improved social behavior in both genotypes and stereotypic behaviors in NS‐Pten KO mice. Rapamycin treatment resulted in a reduction of several measures of activity in the open field test in both genotypes. Rapamycin did not reverse the reduced anxiety behavior in KO mice. These data show the potential clinical use of mTOR inhibitors by showing its administration can reduce the production of autistic‐like behaviors in NS‐Pten KO mice. |
format | Online Article Text |
id | pubmed-10393422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-103934222023-08-02 Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion Narvaiz, David A. Nolan, Suzanne O. Smith, Gregory D. Holley, Andrew J. Reynolds, Conner D. Blandin, Katherine J. Nguyen, Phuoc H. Tran, Doan L. K. Lugo, Joaquin N. Genes Brain Behav Original Articles The mechanistic target of rapamycin (mTOR) pathway is a signaling system integral to neural growth and migration. In both patients and rodent models, mutations to the phosphatase and tensin homolog gene (PTEN) on chromosome 10 results in hyperactivation of the mTOR pathway, as well as seizures, intellectual disabilities and autistic behaviors. Rapamycin, an inhibitor of mTOR, can reverse the epileptic phenotype of neural subset specific Pten knockout (NS‐Pten KO) mice, but its impact on behavior is not known. To determine the behavioral effects of rapamycin, male and female NS‐Pten KO and wildtype (WT) mice were assigned as controls or administered 10 mg/kg of rapamycin for 2 weeks followed by behavioral testing. Rapamycin improved social behavior in both genotypes and stereotypic behaviors in NS‐Pten KO mice. Rapamycin treatment resulted in a reduction of several measures of activity in the open field test in both genotypes. Rapamycin did not reverse the reduced anxiety behavior in KO mice. These data show the potential clinical use of mTOR inhibitors by showing its administration can reduce the production of autistic‐like behaviors in NS‐Pten KO mice. Blackwell Publishing Ltd 2023-06-28 /pmc/articles/PMC10393422/ /pubmed/37376966 http://dx.doi.org/10.1111/gbb.12854 Text en © 2023 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Narvaiz, David A. Nolan, Suzanne O. Smith, Gregory D. Holley, Andrew J. Reynolds, Conner D. Blandin, Katherine J. Nguyen, Phuoc H. Tran, Doan L. K. Lugo, Joaquin N. Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion |
title | Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion |
title_full | Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion |
title_fullStr | Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion |
title_full_unstemmed | Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion |
title_short | Rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific Pten deletion |
title_sort | rapamycin improves social and stereotypic behavior abnormalities induced by pre‐mitotic neuronal subset specific pten deletion |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393422/ https://www.ncbi.nlm.nih.gov/pubmed/37376966 http://dx.doi.org/10.1111/gbb.12854 |
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