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Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders
Open accessAbstract
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.
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“Negr −/− mice have shown irregularities in several brain regions, including reduced brain volume in the hippocampus and have also shown abnormalities in social behavior and non-social interest.20”
From Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions (2021) · cites this paper as [20]
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Metadata
- Authors
- Singh, K., Jayaram, M., Kaare, M., Leidmaa, E., Jagomäe, T., Heinla, I., Hickey, M. A., Kaasik, A., Schäfer, M. K., Innos, J., Lilleväli, K., Philips, M.-A., & Vasar, E.
- Affiliations
- University of Tartu (EE)
- University of Bonn (DE)
- UiT The Arctic University of Norway (NO)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Singh, Katyayani
- ORCID
- Venue
- Scientific Reports
- Published
- 2019-04-01
- Volume
- 9
- Issue
- 1
- Pages
- 5457-5457
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6443666
- OpenAlex
- W2930826460
- Cited by
- 65
- References
- 105
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 12 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 1
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Funders
- European Commission (IUT20-41, 2014‐2020, 2020 ‘, 2014‐2020.4.01.15‐0012, HORIZON2020, 15-0012, 692202)
- Eesti Teadusagentuur (2014-2020, 2014-2020.4.01.15-0012, IUT20-41)
- European Regional Development Fund (IUT20-41, 2014-2020’, 2014-2020.4.01.15-0012, (Project No. 2014-2020.4.01.15-0012), 15-0012, No. 2014-2020.4.01.15-0012)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- NEGR1, adhesion molecules, brain structure, neuroanatomical abnormalities, parvalbumin interneurons, excitation-inhibition balance, social behavior, hyperactivity, social hierarchy, neurite sprouting, neurite outgrowth, thalamic reticular nucleus, mental illness, schizophrenia, autism spectrum disorder, major depressive disorder
- MeSH terms
- Animals, Behavior, Animal, Mental Disorders, Brain, Cell Adhesion Molecules, Neuronal, Mice, Knockout, Mice, Endophenotypes
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