Multitarget neuroprotection by quercetin: Changes in gene expression in two perinatal asphyxia models

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and long-term neurological damage.
• HIE involves complex pathways including energy failure, excitotoxicity, and oxidative stress, leading to cell death.
• Quercetin, a flavonoid, has shown potential neuroprotective effects in preclinical models.

Purpose of the Study:

• To identify neonatal HIE biomarkers.
• To investigate the neuroprotective effects of nanoliposomal quercetin in rat and piglet models of perinatal asphyxia.
• To explore the molecular mechanisms underlying quercetin's protective action.

Main Methods:

• Utilized rat and piglet models of perinatal asphyxia to simulate neonatal HIE.
• Administered nanoliposomal quercetin and assessed mortality rates and protein expression.
• Employed a proteomic approach to analyze changes in protein expression in response to quercetin treatment.
• Measured mRNA levels of hypoxia-inducible factor 1-alpha (HIF-1α) and heme oxygenase-1 (HO-1).

Main Results:

• Nanoliposomal quercetin administration reduced mortality in newborn rats subjected to asphyxia.
• In piglets, quercetin partially counteracted the reduction in HIF-1α mRNA and decreased elevated HO-1 mRNA levels.
• Proteomic analysis revealed quercetin's significant regulation of the glycolytic pathway in both species.
• Identified differentially expressed proteins, including ANP32A, alpha-enolase, dihydropyrimidinase-related proteins, phosphatases, and hnRNPK, as potential HIE markers and targets.

Conclusions:

• Nanoliposomal quercetin demonstrates neuroprotective effects in two distinct mammalian models of HIE.
• Quercetin's mechanism may involve the regulation of HIF-1α, HO-1, and key proteins in energy metabolism.
• The identified proteins represent potential biomarkers for HIE and novel targets for therapeutic intervention.