Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity
A key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model ‘advanced brain aging’ and exhibit a range of behavioral abnormalities. However, the c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/70792 |
| _version_ | 1811155673118932992 |
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| author | Sahab Arinrad Constanze Depp Sophie B Siems Andrew Octavian Sasmita Maria A Eichel Anja Ronnenberg Kurt Hammerschmidt Katja A Lüders Hauke B Werner Hannelore Ehrenreich Klaus-Armin Nave |
| author_facet | Sahab Arinrad Constanze Depp Sophie B Siems Andrew Octavian Sasmita Maria A Eichel Anja Ronnenberg Kurt Hammerschmidt Katja A Lüders Hauke B Werner Hannelore Ehrenreich Klaus-Armin Nave |
| author_sort | Sahab Arinrad |
| collection | DOAJ |
| description | A key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model ‘advanced brain aging’ and exhibit a range of behavioral abnormalities. However, the cognitive assessment of these mutants is problematic because myelin-dependent motor-sensory functions are required for quantitative behavioral readouts. To better understand the role of cortical myelin integrity for higher brain functions, we generated mice lacking Plp1, encoding the major integral myelin membrane protein, selectively in ventricular zone stem cells of the mouse forebrain. In contrast to conventional Plp1 null mutants, subtle myelin defects were restricted to the cortex, hippocampus, and underlying callosal tracts. Moreover, forebrain-specific Plp1 mutants exhibited no defects of basic motor-sensory performance at any age tested. Surprisingly, several behavioral alterations reported for conventional Plp1 null mice (Gould et al., 2018) were absent and even social interactions appeared normal. However, with novel behavioral paradigms, we determined catatonia-like symptoms and isolated executive dysfunction in both genders. This suggests that loss of myelin integrity has an impact on cortical connectivity and underlies specific defects of executive function. These observations are likewise relevant for human neuropsychiatric conditions and other myelin-related diseases. |
| first_indexed | 2024-04-10T04:37:16Z |
| format | Article |
| id | doaj.art-4406315b705a44f782090e70aec23248 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T04:37:16Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4406315b705a44f782090e70aec232482023-03-09T13:48:55ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.70792Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integritySahab Arinrad0https://orcid.org/0000-0002-7083-1358Constanze Depp1https://orcid.org/0000-0003-2868-6932Sophie B Siems2https://orcid.org/0000-0002-7760-2507Andrew Octavian Sasmita3https://orcid.org/0000-0001-7379-6749Maria A Eichel4https://orcid.org/0000-0002-9925-7249Anja Ronnenberg5Kurt Hammerschmidt6Katja A Lüders7Hauke B Werner8https://orcid.org/0000-0002-7710-5738Hannelore Ehrenreich9https://orcid.org/0000-0001-8371-5711Klaus-Armin Nave10https://orcid.org/0000-0001-8724-9666Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyClinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyCognitive Ethology, German Primate Center, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyClinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyNeurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyA key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model ‘advanced brain aging’ and exhibit a range of behavioral abnormalities. However, the cognitive assessment of these mutants is problematic because myelin-dependent motor-sensory functions are required for quantitative behavioral readouts. To better understand the role of cortical myelin integrity for higher brain functions, we generated mice lacking Plp1, encoding the major integral myelin membrane protein, selectively in ventricular zone stem cells of the mouse forebrain. In contrast to conventional Plp1 null mutants, subtle myelin defects were restricted to the cortex, hippocampus, and underlying callosal tracts. Moreover, forebrain-specific Plp1 mutants exhibited no defects of basic motor-sensory performance at any age tested. Surprisingly, several behavioral alterations reported for conventional Plp1 null mice (Gould et al., 2018) were absent and even social interactions appeared normal. However, with novel behavioral paradigms, we determined catatonia-like symptoms and isolated executive dysfunction in both genders. This suggests that loss of myelin integrity has an impact on cortical connectivity and underlies specific defects of executive function. These observations are likewise relevant for human neuropsychiatric conditions and other myelin-related diseases.https://elifesciences.org/articles/70792myelinmouse mutantoligodendrocytesglia functiondisease modelexecutive functions |
| spellingShingle | Sahab Arinrad Constanze Depp Sophie B Siems Andrew Octavian Sasmita Maria A Eichel Anja Ronnenberg Kurt Hammerschmidt Katja A Lüders Hauke B Werner Hannelore Ehrenreich Klaus-Armin Nave Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity eLife myelin mouse mutant oligodendrocytes glia function disease model executive functions |
| title | Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity |
| title_full | Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity |
| title_fullStr | Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity |
| title_full_unstemmed | Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity |
| title_short | Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity |
| title_sort | isolated catatonia like executive dysfunction in mice with forebrain specific loss of myelin integrity |
| topic | myelin mouse mutant oligodendrocytes glia function disease model executive functions |
| url | https://elifesciences.org/articles/70792 |
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