Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation

Author:

Grabowska Anna D.1ORCID,Wątroba Mateusz1,Witkowska Joanna1,Mikulska Agnieszka1,Sepúlveda Nuno23ORCID,Szukiewicz Dariusz1ORCID

Affiliation:

1. Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland

2. Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland

3. CEAUL—Centro de Estatística e Aplicações da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal

Abstract

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.

Funder

Medical University of Warsaw

Fundação para a Ciência e Tecnologia, Portugal

Polish National Agency for Academic Exchange, Poland

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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