Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?
<p>Abstract</p> <p>Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-07-01
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| Series: | Molecular Neurodegeneration |
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| Online Access: | http://www.molecularneurodegeneration.com/content/6/1/55 |
| _version_ | 1818527159586652160 |
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| author | Verkhratsky Alexei Noristani Harun N Olabarria Markel Rodríguez José J |
| author_facet | Verkhratsky Alexei Noristani Harun N Olabarria Markel Rodríguez José J |
| author_sort | Verkhratsky Alexei |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific β-amyloid (Aβ) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in N<sub>v </sub>(number of cell/mm<sup>3</sup>) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes N<sub>v </sub>(33.26%) occurs at 18 months. This N<sub>v </sub>reduction of GS-IR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR N<sub>v </sub>changes are directly associated with the presence of Aβ deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of Aβ. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.</p> |
| first_indexed | 2024-12-11T06:32:28Z |
| format | Article |
| id | doaj.art-cc549dc763874c3a89b0e7bd9d46704f |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-11T06:32:28Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-cc549dc763874c3a89b0e7bd9d46704f2022-12-22T01:17:29ZengBMCMolecular Neurodegeneration1750-13262011-07-01615510.1186/1750-1326-6-55Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?Verkhratsky AlexeiNoristani Harun NOlabarria MarkelRodríguez José J<p>Abstract</p> <p>Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific β-amyloid (Aβ) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in N<sub>v </sub>(number of cell/mm<sup>3</sup>) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes N<sub>v </sub>(33.26%) occurs at 18 months. This N<sub>v </sub>reduction of GS-IR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR N<sub>v </sub>changes are directly associated with the presence of Aβ deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of Aβ. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.</p>http://www.molecularneurodegeneration.com/content/6/1/55AstrogliaAlzheimer's diseaseglutamine synthetaseGFAPamyloid betaexcitotoxicityhippocampusplasticity |
| spellingShingle | Verkhratsky Alexei Noristani Harun N Olabarria Markel Rodríguez José J Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? Molecular Neurodegeneration Astroglia Alzheimer's disease glutamine synthetase GFAP amyloid beta excitotoxicity hippocampus plasticity |
| title | Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? |
| title_full | Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? |
| title_fullStr | Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? |
| title_full_unstemmed | Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? |
| title_short | Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? |
| title_sort | age dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic alzheimer s disease mouse model mechanism for deficient glutamatergic transmission |
| topic | Astroglia Alzheimer's disease glutamine synthetase GFAP amyloid beta excitotoxicity hippocampus plasticity |
| url | http://www.molecularneurodegeneration.com/content/6/1/55 |
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