Beneficial Effects of Snail Helix aspersa Extract in an Experimental Model of Alzheimer’s Type Dementia

Article type: Research Article

Authors: Tancheva, Lyubka^{a; b} | Lazarova, Maria^a | Velkova, Lyudmila^c | Dolashki, Alexander^c | Uzunova, Diamara^a | Minchev, Borislav^a | Petkova-Kirova, Polina^a | Hassanova, Yozljam^a | Gavrilova, Petja^a | Tasheva, Krasimira^d | Taseva, Teodora^d | Hodzhev, Yordan^e | Atanasov, Atanas G.^{f; g; h} | Stefanova, Miroslava^a | Alexandrova, Albena^a | Tzvetanova, Elina^a | Atanasov, Ventseslav^c | Kalfin, Reni^{a; i; *} | Dolashka, Pavlina^c

Affiliations: [a] Institute of Neurobiology, Bulgarian Academy of Science, Sofia, Bulgaria | [b] Weston Professor of Weizmann Institute of Science, Israel | [c] Institute of Organic Chemistry with Center for Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria | [d] Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Sofia, Bulgaria | [e] National Center for Infectious and Parasitic Diseases, Sofia, Bulgaria | [f] Ludwig Boltzmann Institute for Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria | [g] Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland | [h] Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria | [i] Department of Healthcare, South-West University “Neofit Rilski”, Blagoevgrad, Bulgaria

Correspondence: [*] Correspondence to: Reni Kalfin, Institute of Neurobiology, Bulgarian Academy of Science, Acad. G. Bonchev Str., Block 23, Sofia 1113, Bulgaria. E-mail: reni_kalfin@abv.bg.

Abstract: Background:Alzheimer’s disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders. Objective:The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer’s type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated. Methods:SE (0.5 mL/100 g) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2 mg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined. Results:We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it. Conclusion:Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer’s type dementia.

Keywords: Antioxidant system, BDNF, cholinergic function, CREB, scopolamine, snail Helix aspersa

DOI: 10.3233/JAD-215693

Journal: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 155-175, 2022