Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron–astrocyte–microglia dysregulation
| العنوان: | Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron–astrocyte–microglia dysregulation |
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| المؤلفون: | Rui Li, Pak C. Sham, Qi Li, Zheng-Hua Xiang, Rigil K Yeung, Chok-King Hui, Ming-Qi Qiao, Shui Ying Tsang, Timothy Y. C. Ho, Hong Xue |
| المصدر: | Translational Psychiatry, Vol 8, Iss 1, Pp 1-14 (2018) Translational Psychiatry |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Interneuron, Hippocampus, Polymorphism, Single Nucleotide, Article, lcsh:RC321-571, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Receptors, GABA, Interneurons, Internal medicine, medicine, Animals, Genetic Predisposition to Disease, Pentylenetetrazol, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Prepulse inhibition, Neuroinflammation, Mice, Knockout, Microglia, biology, Prepulse Inhibition, Dystrophy, Receptors, GABA-A, Risperidone, 030227 psychiatry, Mice, Inbred C57BL, Psychiatry and Mental health, Phenotype, Endocrinology, medicine.anatomical_structure, Astrocytes, Behavior Rating Scale, Knockout mouse, Schizophrenia, biology.protein, Female, 030217 neurology & neurosurgery, Parvalbumin, Antipsychotic Agents, medicine.drug |
| الوصف: | Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure. In addition, the KO mice were highly susceptible to audiogenic epilepsy. Some of the behavioral phenotypes showed evidence of imprinting, gender effect and amelioration by the antipsychotic risperidone, and the audiogenic epilepsy was inhibited by the antiepileptic diazepam. GABAergic parvalbumin (PV)-positive interneuron dystrophy, astrocyte dystrophy, and extensive microglia activation were observed in the frontotemporal corticolimbic regions, and reduction of newborn neurons was observed in the hippocampus by immunohistochemical staining. The neuroinflammation indicated by microglial activation was accompanied by elevated brain levels of oxidative stress marker malondialdehyde (MDA) and the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These extensive schizophrenia-like and comorbid phenotypes brought about by Gabrb2 knockout, in conjunction with our previous findings on GABRB2 association with schizophrenia, support a pivotal role of GABRB2 in schizophrenia etiology. |
| اللغة: | English |
| تدمد: | 2158-3188 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::699d56d0cc786accd9fb93abe5156c18Test https://doaj.org/article/305aaff047fd434bad2a57fe1e4a0635Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....699d56d0cc786accd9fb93abe5156c18 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21583188 |
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