Neuroprotective Effects of Dehydroepiandrosterone Sulphate Against Aβ Toxicity and Accumulation in Cellular and Animal Model of Alzheimer’s Disease

Vuić, Barbara; Miloš, Tina; Kvak, Erika; Konjevod, Marcela; Tudor, Lucija; Farkas, Szidónia; Nedić Erjavec, Gordana; Nikolac Perković, Matea; Zelena, Dora; Švob Štrac, Dubravka (2025) Neuroprotective Effects of Dehydroepiandrosterone Sulphate Against Aβ Toxicity and Accumulation in Cellular and Animal Model of Alzheimer’s Disease. Biomedicines, 13 (2). ISSN 2227-9059

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Abstract

Background/Objectives: Beneficial effects of neurosteroid dehydroepiandrosterone sulphate (DHEAS) on cognition, emotions and behavior have been previously reported, suggesting its potential in the prevention and treatment of various neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease (AD). This study aimed to investigate the potential neuroprotective actions of DHEAS against Aβ toxicity in both cellular and animal models of AD. Methods: After optimizing the AD model in vitro, we investigated the DHEAS effects on the viability and death of primary mouse neurons exposed to toxic Aβ42 oligomers for 24 h. In order to extend our research to an in vivo study, we further tested the acute effects of intraperitoneal DHEAS administration on the Aβ plaque density in different brain regions of 3xTg-AD mice, an animal model of AD. Results: In cell culture, DHEAS hampered the decrease in the neuronal viability caused by toxic Aβ oligomers, primarily by influencing mitochondrial function and apoptosis. DHEAS also counteracted the increase in the mRNA expression of selected genes (PI3K, Akt, Bcl2, Bax), induced in neuronal culture by treatment with Aβ42 oligomers. Obtained data suggested the involvement of mitochondria, caspases 3 and 7, as well as the PI3K/Akt and Bcl2 signaling network in the antiapoptotic properties of DHEAS in neurons. Forty-eight hours after DHEAS treatment, a significantly lower number of Aβ plaques was observed in the motor cortex but not in other brain areas of 3xTg-AD mice. Conclusions: Results indicated potential neuroprotective effects of DHEAS against Aβ toxicity and accumulation, suggesting that DHEAS supplementation should be further studied as a novel option for AD prevention and/or treatment.

Item Type:	Article
Uncontrolled Keywords:	Aβ oligomers; Alzheimer’s disease; dehydroepiandrosterone sulphate; neuroprotection; primary neurons; 3xTg-AD mice
Subjects:	BIOMEDICINE AND HEALTHCARE
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Terapijski potencijal neurosteroida i neurotrofina u demenciji-TePoNeDe Dubravka Švob Štrac; Ninoslav Mimica; Suzana Uzun; Oliver Kozumplik; Julija Erhardt; Ana-Marija Domijan; Dora Zelena; Erika Pinter; Coral Barbas IP-2019-04-6100 HRZZ
Depositing User:	Lorena Palameta
Date Deposited:	07 Jul 2025 12:40
URI:	http://fulir.irb.hr/id/eprint/9893
DOI:	10.3390/biomedicines13020432

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