Prenatal Intake of Omega-3 Promotes Wnt/β-catenin Signaling Pathway, and Preserves Integrity of the Blood-brain Barrier in Preeclamptic Rats
Overview
Authors
Affiliations
Background: Preeclampsia is a systemic, multi-organ endotheliopathy, associated with oxidative injury to the blood-brain barrier (BBB). Preeclampsia initiates a cascade of events that include neuroinflammation. Recently, it was documented that Wnt/β-catenin signaling pathway exerts neuroprotective effects and maintain BBB integrity. We investigate the protective effect of omega-3 against neurovascular complication of preeclampsia and its relation to Wnt/β-catenin signaling pathway.
Methodology: After confirmation of day 0 pregnancy (G0), 24 adult pregnant female Wistar rats were divided into four groups control pregnant, pregnant supplemented with omega-3, preeclampsia (PE); female rats received N (ω)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg/day SC from day 7 to day 16 of pregnancy for induction of preeclampsia) and PE rats supplemented with omega-3. The intake of omega-3 started on day zero (0) of pregnancy until the end of the study (144 mg/kg\day orally).
Results: We found that omega-3 supplementation significantly improved cognitive functions and EEG amplitude, decreased blood pressure, water contents of brain tissues, sFlt-1, oxidative stress, proteinuria, and enhanced Wnt\β-catenin proteins. Histological examination showed improved cerebral microangiopathy, increased expression of claudin-1 and -3, CD31, and VEGF in the cerebral cortical microvasculature and choroid plexus in PE rats treated with omega-3. A positive correlation between protein expression level of Wnt \β-catenin and cognitive functions, and a negative correlation between claudin-5 relative expression, claudin-1 and -3 area % from one side and water content of the brain tissues from the other side were observed.
Conclusion: Wnt/β-catenin signaling pathway suspected to have an important role to improve BBB integrity. Neuroprotective, antioxidant, and anti-inflammatory effects of omega-3 were observed and can be suggested as protective supplementation for preeclampsia.
Das S, Varshney R, Farriester J, Kyere-Davies G, Martinez A, Hill K bioRxiv. 2024; .
PMID: 39314382 PMC: 11419096. DOI: 10.1101/2024.09.09.611047.
Salk S, Yurtcu N, Cetin A Turk J Obstet Gynecol. 2022; 19(4):268-274.
PMID: 36511565 PMC: 9748862. DOI: 10.4274/tjod.galenos.2022.38932.
The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health.
de Alwis N, Binder N, Beard S, Mangwiro Y, Kadife E, Cuffe J Life Sci Alliance. 2022; 5(12).
PMID: 36260752 PMC: 9356384. DOI: 10.26508/lsa.202201517.
Guo K, Li W, Wang Z, He L, Feng Y, Liu H Cell Cycle. 2022; 21(21):2223-2238.
PMID: 35792905 PMC: 9586659. DOI: 10.1080/15384101.2022.2092814.
Vogtmann R, Burk L, Serdar M, Kimmig R, Bendix I, Gellhaus A Oxid Med Cell Longev. 2022; 2022:3024032.
PMID: 35693702 PMC: 9184195. DOI: 10.1155/2022/3024032.