Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation
The flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, a...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11640 |
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| author | Anna D. Grabowska Mateusz Wątroba Joanna Witkowska Agnieszka Mikulska Nuno Sepúlveda Dariusz Szukiewicz |
| author_facet | Anna D. Grabowska Mateusz Wątroba Joanna Witkowska Agnieszka Mikulska Nuno Sepúlveda Dariusz Szukiewicz |
| author_sort | Anna D. Grabowska |
| collection | DOAJ |
| description | The flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia. |
| first_indexed | 2024-03-11T00:59:29Z |
| format | Article |
| id | doaj.art-3519e9c472534ff2a19b0a059a485797 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:59:29Z |
| publishDate | 2023-07-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3519e9c472534ff2a19b0a059a4857972023-11-18T19:42:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141164010.3390/ijms241411640Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to NeuroinflammationAnna D. Grabowska0Mateusz Wątroba1Joanna Witkowska2Agnieszka Mikulska3Nuno Sepúlveda4Dariusz Szukiewicz5Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, PolandLaboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, PolandLaboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, PolandLaboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, PolandFaculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, PolandLaboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, PolandThe flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia.https://www.mdpi.com/1422-0067/24/14/11640blood–brain barrierastrocytesglycemianeuroinflammationsirtuin 1resveratrol |
| spellingShingle | Anna D. Grabowska Mateusz Wątroba Joanna Witkowska Agnieszka Mikulska Nuno Sepúlveda Dariusz Szukiewicz Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation International Journal of Molecular Sciences blood–brain barrier astrocytes glycemia neuroinflammation sirtuin 1 resveratrol |
| title | Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation |
| title_full | Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation |
| title_fullStr | Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation |
| title_full_unstemmed | Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation |
| title_short | Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation |
| title_sort | interplay between systemic glycemia and neuroprotective activity of resveratrol in modulating astrocyte sirt1 response to neuroinflammation |
| topic | blood–brain barrier astrocytes glycemia neuroinflammation sirtuin 1 resveratrol |
| url | https://www.mdpi.com/1422-0067/24/14/11640 |
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