Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures
The tissue renin–angiotensin system (RAS) has been shown to be involved in prooxidative and proinflammatory changes observed in aging and aging-related diseases such as dopaminergic degeneration in Parkinson’s disease (PD). We studied the activation of the NLRP3 inflammasome in the <i>substant...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/2/329 |
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| author | Aloia Quijano Carmen Diaz-Ruiz Andrea Lopez-Lopez Begoña Villar-Cheda Ana Muñoz Ana I. Rodriguez-Perez Jose L. Labandeira-Garcia |
| author_facet | Aloia Quijano Carmen Diaz-Ruiz Andrea Lopez-Lopez Begoña Villar-Cheda Ana Muñoz Ana I. Rodriguez-Perez Jose L. Labandeira-Garcia |
| author_sort | Aloia Quijano |
| collection | DOAJ |
| description | The tissue renin–angiotensin system (RAS) has been shown to be involved in prooxidative and proinflammatory changes observed in aging and aging-related diseases such as dopaminergic degeneration in Parkinson’s disease (PD). We studied the activation of the NLRP3 inflammasome in the <i>substantia nigra</i> with aging and early stages of dopaminergic degeneration in PD models and, particularly, if the brain RAS, via its prooxidative proinflammatory angiotensin II (AngII) type 1 (AT1) receptors, mediates the inflammasome activation. <i>Nigras</i> from aged rats and mice and 6-hydroxydopamine PD models showed upregulation in transcription of inflammasome-related components (NLRP3, pro-IL1β and pro-IL18) and IL1β and IL18 protein levels, which was inhibited by the AT1 receptor antagonist candesartan. The role of the AngII/AT1 axis in inflammasome activation was further confirmed in rats intraventricularly injected with AngII, and in primary mesencephalic cultures treated with 6-hydroxydopamine, which showed inflammasome activation that was blocked by candesartan. Observations in the <i>nigra</i> of young and aged AT1 and AT2 knockout mice confirmed the major role of AT1 receptors in nigral inflammasome activation. In conclusion, the inflammasome is upregulated by aging and dopaminergic degeneration in the <i>substantia nigra</i>, possibly related with a decrease in dopamine levels, and it is mediated by the AngII/AT1 axis. |
| first_indexed | 2024-03-09T22:44:50Z |
| format | Article |
| id | doaj.art-bba0dc916a3b430fa3412779f6a057a2 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T22:44:50Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-bba0dc916a3b430fa3412779f6a057a22023-11-23T18:32:06ZengMDPI AGAntioxidants2076-39212022-02-0111232910.3390/antiox11020329Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic CulturesAloia Quijano0Carmen Diaz-Ruiz1Andrea Lopez-Lopez2Begoña Villar-Cheda3Ana Muñoz4Ana I. Rodriguez-Perez5Jose L. Labandeira-Garcia6Laboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainLaboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainLaboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainLaboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainLaboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainLaboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainLaboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainThe tissue renin–angiotensin system (RAS) has been shown to be involved in prooxidative and proinflammatory changes observed in aging and aging-related diseases such as dopaminergic degeneration in Parkinson’s disease (PD). We studied the activation of the NLRP3 inflammasome in the <i>substantia nigra</i> with aging and early stages of dopaminergic degeneration in PD models and, particularly, if the brain RAS, via its prooxidative proinflammatory angiotensin II (AngII) type 1 (AT1) receptors, mediates the inflammasome activation. <i>Nigras</i> from aged rats and mice and 6-hydroxydopamine PD models showed upregulation in transcription of inflammasome-related components (NLRP3, pro-IL1β and pro-IL18) and IL1β and IL18 protein levels, which was inhibited by the AT1 receptor antagonist candesartan. The role of the AngII/AT1 axis in inflammasome activation was further confirmed in rats intraventricularly injected with AngII, and in primary mesencephalic cultures treated with 6-hydroxydopamine, which showed inflammasome activation that was blocked by candesartan. Observations in the <i>nigra</i> of young and aged AT1 and AT2 knockout mice confirmed the major role of AT1 receptors in nigral inflammasome activation. In conclusion, the inflammasome is upregulated by aging and dopaminergic degeneration in the <i>substantia nigra</i>, possibly related with a decrease in dopamine levels, and it is mediated by the AngII/AT1 axis.https://www.mdpi.com/2076-3921/11/2/329ageddopamineinflammationinflammagingneuroinflammationoxidative stress |
| spellingShingle | Aloia Quijano Carmen Diaz-Ruiz Andrea Lopez-Lopez Begoña Villar-Cheda Ana Muñoz Ana I. Rodriguez-Perez Jose L. Labandeira-Garcia Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures Antioxidants aged dopamine inflammation inflammaging neuroinflammation oxidative stress |
| title | Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures |
| title_full | Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures |
| title_fullStr | Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures |
| title_full_unstemmed | Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures |
| title_short | Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the <i>Substantia Nigra</i> of Male Rodents and Primary Mesencephalic Cultures |
| title_sort | angiotensin type 1 receptor inhibition reduces nlrp3 inflammasome upregulation induced by aging and neurodegeneration in the i substantia nigra i of male rodents and primary mesencephalic cultures |
| topic | aged dopamine inflammation inflammaging neuroinflammation oxidative stress |
| url | https://www.mdpi.com/2076-3921/11/2/329 |
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