Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders

被引：36

作者：

Singh, Katyayani ^{[1
,2
]}

Jayaram, Mohan ^{[1
,2
]}

Kaare, Maria ^{[1
,2
]}

Leidmaa, Este ^{[3
]}

Jagomae, Toomas ^{[1
,2
]}

Heinla, Indrek ^{[4
]}

Hickey, Miriam A. ^{[5
]}

Kaasik, Allen ^{[5
]}

Schaefer, Michael K. ^{[6
,7
]}

Innos, Jurgen ^{[1
,2
]}

Lillevali, Kersti ^{[1
,2
]}

Philips, Mari-Anne ^{[1
,2
]}

Vasar, Eero ^{[1
,2
]}

机构：

[1] Univ Tartu, Inst Biomed & Translat Med, Dept Physiol, 19 Ravila St, EE-50411 Tartu, Estonia

[2] Univ Tartu, Ctr Excellence Genom & Translat Med, 19 Ravila St, EE-50411 Tartu, Estonia

[3] Univ Bonn, Inst Mol Psychiat, Sigmund Freud Str 25, D-53127 Bonn, Germany

[4] UiT Arctic Univ Norway, Dept Psychol, Postboks 6050 Langnes, N-9037 Tromso, Norway

[5] Univ Tartu, Inst Biomed & Translat Med, Dept Pharmacol, 19 Ravila St, EE-50411 Tartu, Estonia

[6] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Anesthesiol, Mainz, Germany

[7] Johannes Gutenberg Univ Mainz, Focus Program Translat Neurosci FTN, Mainz, Germany

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

基金：

欧盟地平线“2020”;

关键词：

AUTISM SPECTRUM DISORDER; VENTRICULAR ENLARGEMENT; NEURITE OUTGROWTH; CORPUS-CALLOSUM; IGLON FAMILY; NEUROANATOMICAL PHENOTYPES; MAJOR DEPRESSION; WHITE-MATTER; SCHIZOPHRENIA; MICE;

D O I：

10.1038/s41598-019-41991-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neuronal growth regulator 1 (NEGRI.) 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 Negri deficiency on brain morphology, neuronal properties and social behavior of mice. In situ hybridization shows Negri 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, Negri 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.

引用

页数：15

共 1 条

[1] CD9 of mouse brain is implicated in neurite outgrowth and cell migration in vitro and is associated with the alpha 6/beta 1 integrin and the neural adhesion molecule L1
Schmidt, C
Kunemund, V
Wintergerst, ES
Schmitz, B
Schachner, M
JOURNAL OF NEUROSCIENCE RESEARCH, 1996, 43 (01) : 12 - 31

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