Pten haploinsufficiency disrupts scaling across brain areas during development in mice
| Autor: | Damon T. Page, Amy E. Clipperton-Allen, Jason P. Lerch, Jacob Ellegood, Jenna Levy, Ori S. Cohen, Aya Zucca, Massimiliano Aceti |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Mice 129 Strain Autism Spectrum Disorder Cell Haploinsufficiency Molecular neuroscience Article lcsh:RC321-571 White matter Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Animals Humans PTEN lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cells Cultured Biological Psychiatry Cerebral Cortex biology Extramural PTEN Phosphohydrolase Autism spectrum disorders medicine.disease Magnetic Resonance Imaging White Matter Disease Models Animal Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Autism spectrum disorder biology.protein Autism Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Vol 9, Iss 1, Pp 1-14 (2019) |
| ISSN: | 2158-3188 |
| Popis: | Haploinsufficiency for PTEN is a cause of autism spectrum disorder and brain overgrowth; however, it is not known if PTEN mutations disrupt scaling across brain areas during development. To address this question, we used magnetic resonance imaging to analyze brains of male Pten haploinsufficient (Pten+/−) mice and wild-type littermates during early postnatal development and adulthood. Adult Pten+/− mice display a consistent pattern of abnormal scaling across brain areas, with white matter (WM) areas being particularly affected. This regional and WM enlargement recapitulates structural abnormalities found in individuals with PTEN haploinsufficiency and autism. Early postnatal Pten+/− mice do not display the same pattern, instead exhibiting greater variability across mice and brain regions than controls. This suggests that Pten haploinsufficiency may desynchronize growth across brain regions during early development before stabilizing by maturity. Pten+/− cortical cultures display increased proliferation of glial cell populations, indicating a potential substrate of WM enlargement, and provide a platform for testing candidate therapeutics. Pten haploinsufficiency dysregulates coordinated growth across brain regions during development. This results in abnormally scaled brain areas and associated behavioral deficits, potentially explaining the relationship between PTEN mutations and neurodevelopmental disorders. |
| Databáze: | OpenAIRE |
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