Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia
Abstract Background Stroke is a leading cause of death and disability worldwide. A major factor in brain damage following ischemia is excitotoxicity caused by elevated levels of the neurotransmitter glutamate. In the brain, glutamate homeostasis is a primary function of astrocytes. Amburana cearensi...
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BMC
2023-05-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-023-03959-0 |
| _version_ | 1797827746781462528 |
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| author | Rafael Short Ferreira Paulo Roberto Ribeiro Juliana Helena Castro e Silva Juliana Bender Hoppe Monique Marylin Alves de Almeida Beatriz Correia de Lima Ferreira Gustavo Borges Andrade Suzana Braga de Souza Luzimar Gonzaga Ferdandez Maria de Fátima Dias Costa Christianne Gazzana Salbego Andrea Domenico Rivera Aline Longoni Adriano Martimbianco de Assis Francesca Pieropan José Cláudio Fonseca Moreira Silvia Lima Costa Arthur Morgan Butt Victor Diogenes Amaral da Silva |
| author_facet | Rafael Short Ferreira Paulo Roberto Ribeiro Juliana Helena Castro e Silva Juliana Bender Hoppe Monique Marylin Alves de Almeida Beatriz Correia de Lima Ferreira Gustavo Borges Andrade Suzana Braga de Souza Luzimar Gonzaga Ferdandez Maria de Fátima Dias Costa Christianne Gazzana Salbego Andrea Domenico Rivera Aline Longoni Adriano Martimbianco de Assis Francesca Pieropan José Cláudio Fonseca Moreira Silvia Lima Costa Arthur Morgan Butt Victor Diogenes Amaral da Silva |
| author_sort | Rafael Short Ferreira |
| collection | DOAJ |
| description | Abstract Background Stroke is a leading cause of death and disability worldwide. A major factor in brain damage following ischemia is excitotoxicity caused by elevated levels of the neurotransmitter glutamate. In the brain, glutamate homeostasis is a primary function of astrocytes. Amburana cearensis has long been used in folk medicine and seed extract obtained with dichloromethane (EDAC) have previously been shown to exhibit cytoprotective activity in vitro. The aim of the present study was to analyse the activity of EDAC in hippocampal brain slices. Methods We prepared a dichloromethane extract (EDAC) from A. cearensis seeds and characterized the chemical constituents by 1H and 13C-NMR. Hippocampal slices from P6-8 or P90 Wistar rats were used for cell viability assay or glutamate uptake test. Hippocampal slices from P10-12 transgenic mice SOX10-EGFP and GFAP-EGFP and immunofluorescence for GS, GLAST and GLT1 were used to study oligodendrocytes and astrocytes. Results Astrocytes play a critical role in glutamate homeostasis and we provide immunohistochemical evidence that in excitotoxicity EDAC increased expression of glutamate transporters and glutamine synthetase, which is essential for detoxifying glutamate. Next, we directly examined astrocytes using transgenic mice in which glial fibrillary acidic protein (GFAP) drives expression of enhanced green fluorescence protein (EGFP) and show that glutamate excitotoxicity caused a decrease in GFAP-EGFP and that EDAC protected against this loss. This was examined further in the oxygen–glucose deprivation (OGD) model of ischemia, where EDAC caused an increase in astrocytic process branching, resulting in an increase in GFAP-EGFP. Using SOX10-EGFP reporter mice, we show that the acute response of oligodendrocytes to OGD in hippocampal slices is a marked loss of their processes and EDAC protected oligodendrocytes against this damage. Conclusion This study provides evidence that EDAC is cytoprotective against ischemia and glutamate excitotoxicity by modulating astrocyte responses and stimulating their glutamate homeostatic mechanisms. |
| first_indexed | 2024-04-09T12:53:18Z |
| format | Article |
| id | doaj.art-f8cd2f74dfeb4682a3778b317704dcf5 |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-04-09T12:53:18Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-f8cd2f74dfeb4682a3778b317704dcf52023-05-14T11:08:09ZengBMCBMC Complementary Medicine and Therapies2662-76712023-05-0123111710.1186/s12906-023-03959-0Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemiaRafael Short Ferreira0Paulo Roberto Ribeiro1Juliana Helena Castro e Silva2Juliana Bender Hoppe3Monique Marylin Alves de Almeida4Beatriz Correia de Lima Ferreira5Gustavo Borges Andrade6Suzana Braga de Souza7Luzimar Gonzaga Ferdandez8Maria de Fátima Dias Costa9Christianne Gazzana Salbego10Andrea Domenico Rivera11Aline Longoni12Adriano Martimbianco de Assis13Francesca Pieropan14José Cláudio Fonseca Moreira15Silvia Lima Costa16Arthur Morgan Butt17Victor Diogenes Amaral da Silva18Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBAMetabolomics Research Group, Department of Organic Chemistry, Chemistry Institute, Federal University of BahiaLaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBADepartment of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande Do SulLaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBALaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBALaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBALaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBABiochemistry, Biotechnology and Bioproducts Laboratory, Institute of Health Sciences, Federal University of BahiaLaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBADepartment of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande Do SulSchool of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s BuildingHealth Sciences Centre, Post-Graduate Program in Health and Behaviour, Catholic University of PelotasHealth Sciences Centre, Post-Graduate Program in Health and Behaviour, Catholic University of PelotasSchool of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s BuildingDepartment of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande Do SulLaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBASchool of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s BuildingLaboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia - UFBAAbstract Background Stroke is a leading cause of death and disability worldwide. A major factor in brain damage following ischemia is excitotoxicity caused by elevated levels of the neurotransmitter glutamate. In the brain, glutamate homeostasis is a primary function of astrocytes. Amburana cearensis has long been used in folk medicine and seed extract obtained with dichloromethane (EDAC) have previously been shown to exhibit cytoprotective activity in vitro. The aim of the present study was to analyse the activity of EDAC in hippocampal brain slices. Methods We prepared a dichloromethane extract (EDAC) from A. cearensis seeds and characterized the chemical constituents by 1H and 13C-NMR. Hippocampal slices from P6-8 or P90 Wistar rats were used for cell viability assay or glutamate uptake test. Hippocampal slices from P10-12 transgenic mice SOX10-EGFP and GFAP-EGFP and immunofluorescence for GS, GLAST and GLT1 were used to study oligodendrocytes and astrocytes. Results Astrocytes play a critical role in glutamate homeostasis and we provide immunohistochemical evidence that in excitotoxicity EDAC increased expression of glutamate transporters and glutamine synthetase, which is essential for detoxifying glutamate. Next, we directly examined astrocytes using transgenic mice in which glial fibrillary acidic protein (GFAP) drives expression of enhanced green fluorescence protein (EGFP) and show that glutamate excitotoxicity caused a decrease in GFAP-EGFP and that EDAC protected against this loss. This was examined further in the oxygen–glucose deprivation (OGD) model of ischemia, where EDAC caused an increase in astrocytic process branching, resulting in an increase in GFAP-EGFP. Using SOX10-EGFP reporter mice, we show that the acute response of oligodendrocytes to OGD in hippocampal slices is a marked loss of their processes and EDAC protected oligodendrocytes against this damage. Conclusion This study provides evidence that EDAC is cytoprotective against ischemia and glutamate excitotoxicity by modulating astrocyte responses and stimulating their glutamate homeostatic mechanisms.https://doi.org/10.1186/s12906-023-03959-0Amburana cearensisHippocampusOligodendrocyteAstrocyteStroke |
| spellingShingle | Rafael Short Ferreira Paulo Roberto Ribeiro Juliana Helena Castro e Silva Juliana Bender Hoppe Monique Marylin Alves de Almeida Beatriz Correia de Lima Ferreira Gustavo Borges Andrade Suzana Braga de Souza Luzimar Gonzaga Ferdandez Maria de Fátima Dias Costa Christianne Gazzana Salbego Andrea Domenico Rivera Aline Longoni Adriano Martimbianco de Assis Francesca Pieropan José Cláudio Fonseca Moreira Silvia Lima Costa Arthur Morgan Butt Victor Diogenes Amaral da Silva Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia BMC Complementary Medicine and Therapies Amburana cearensis Hippocampus Oligodendrocyte Astrocyte Stroke |
| title | Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia |
| title_full | Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia |
| title_fullStr | Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia |
| title_full_unstemmed | Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia |
| title_short | Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia |
| title_sort | amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia |
| topic | Amburana cearensis Hippocampus Oligodendrocyte Astrocyte Stroke |
| url | https://doi.org/10.1186/s12906-023-03959-0 |
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