Imbalance between Glutamate and GABA in Fmr1 Knockout Astrocytes Influences Neuronal Development
| Autor: | Yu-Jiao Li, Qi Yang, Lu Wang, Le Yang, Qi-xin Shi, Shi-meng Zhou, Ming-gao Zhao, Kun Zhang, Yan Wang, Liu-kun Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities lcsh:QH426-470 fragile X syndrome FMRP astrocyte glutamate oxidative stress GABA Biology Vigabatrin Article 03 medical and health sciences GABA transaminase 0302 clinical medicine Internal medicine Genetics medicine Genetics (clinical) Glutaminase Glutamate receptor Neurotoxicity medicine.disease FMR1 nervous system diseases lcsh:Genetics 030104 developmental biology medicine.anatomical_structure Endocrinology nervous system Monoamine oxidase B 030217 neurology & neurosurgery Astrocyte medicine.drug |
| Zdroj: | Genes; Volume 7; Issue 8; Pages: 45 Genes Genes, Vol 7, Iss 8, p 45 (2016) |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes7080045 |
| Popis: | Fragile X syndrome (FXS) is a form of inherited mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), the product of the Fmr1 gene. Numerous studies have shown that FMRP expression in astrocytes is important in the development of FXS. Although astrocytes affect neuronal dendrite development in Fmr1 knockout (KO) mice, the factors released by astrocytes are still unclear. We cultured wild type (WT) cortical neurons in astrocyte-conditioned medium (ACM) from WT or Fmr1 KO mice. Immunocytochemistry and Western blotting were performed to detect the dendritic growth of both WT and KO neurons. We determined glutamate and γ-aminobutyric acid (GABA) levels using high-performance liquid chromatography (HPLC). The total neuronal dendritic length was reduced when cultured in the Fmr1 KO ACM. This neurotoxicity was triggered by an imbalanced release of glutamate and GABA from Fmr1 KO astrocytes. We found increased glutaminase and GABA transaminase (GABA-T) expression and decreased monoamine oxidase B expression in Fmr1 KO astrocytes. The elevated levels of glutamate contributed to oxidative stress in the cultured neurons. Vigabatrin (VGB), a GABA-T inhibitor, reversed the changes caused by glutamate and GABA release in Fmr1 KO astrocytes and the abnormal behaviors in Fmr1 KO mice. Our results indicate that the imbalance in the astrocytic glutamate and GABA release may be involved in the neuropathology and the underlying symptoms of FXS, and provides a therapeutic target for treatment. |
| Databáze: | OpenAIRE |
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