Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders
| العنوان: | Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders |
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| المؤلفون: | Miriam A Hickey, Katyayani Singh, Toomas Jagomäe, Kersti Lilleväli, Este Leidmaa, Eero Vasar, Mohan Jayaram, Michael K. E. Schäfer, Allen Kaasik, Mari-Anne Philips, Maria Kaare, Jürgen Innos, Indrek Heinla |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-15 (2019) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Endophenotypes, VDP::Social science: 200::Psychology: 260, Cell Adhesion Molecules, Neuronal, Thalamus, lcsh:Medicine, Biology, Inhibitory postsynaptic potential, Corpus callosum, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, lcsh:Science, Psychiatry, Mice, Knockout, Multidisciplinary, Behavior, Animal, Neuronal growth regulator 1, Cell adhesion molecule, Mental Disorders, lcsh:R, Brain morphometry, Brain, 030104 developmental biology, Globus pallidus, nervous system, VDP::Samfunnsvitenskap: 200::Psykologi: 260, lcsh:Q, Neural cell adhesion molecule, 030217 neurology & neurosurgery |
| الوصف: | Neuronal growth regulator 1 (NEGR1) belongs to the immunoglobulin (IgLON) superfamily of cell adhesion molecules involved in cortical layering. Recent functional and genomic studies implicate the role of NEGR1 in a wide spectrum of psychiatric disorders, such as major depression, schizophrenia and autism. Here, we investigated the impact of Negr1 deficiency on brain morphology, neuronal properties and social behavior of mice. In situ hybridization shows Negr1 expression in the brain nuclei which are central modulators of cortical-subcortical connectivity such as the island of Calleja and the reticular nucleus of thalamus. Brain morphological analysis revealed neuroanatomical abnormalities in Negr1−/− mice, including enlargement of ventricles and decrease in the volume of the whole brain, corpus callosum, globus pallidus and hippocampus. Furthermore, decreased number of parvalbumin-positive inhibitory interneurons was evident in Negr1−/− hippocampi. Behaviorally, Negr1−/− mice displayed hyperactivity in social interactions and impairments in social hierarchy. Finally, Negr1 deficiency resulted in disrupted neurite sprouting during neuritogenesis. Our results provide evidence that NEGR1 is required for balancing the ratio of excitatory/inhibitory neurons and proper formation of brain structures, which is prerequisite for adaptive behavioral profiles. Therefore, Negr1−/− mice have a high potential to provide new insights into the neural mechanisms of neuropsychiatric disorders. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb3f8167902958e7fdbcabf5ed982e95 https://doi.org/10.1038/s41598-019-41991-8 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bb3f8167902958e7fdbcabf5ed982e95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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