Long-Term Administration of Vespa velutina nigrithorax Venom Ameliorates Alzheimer’s Phenotypes in 5xFAD Transgenic Mice
Abstract
:1. Introduction
2. Results
2.1. WV Treatment Improves Learning and Memory Function in 5xFAD Tg Mice
2.2. WV Treatment Ameliorates Histological Damage and Aβ Deposition in the Hippocampus
2.3. WV Treatment Decreases the Expression of Inflammation-Associated Markers in the Hippocampus and Cerebral Cortex
2.4. WV Treatment Attenuates Oxidative Stress in 5xFAD Mice
3. Discussion
4. Materials and Methods
4.1. Preparation of WV and BV
4.2. Experimental Animals
4.3. Genotyping
4.4. Experimental Design
4.5. Behavioral Tests
4.6. Western Blotting and Analysis
4.7. Measurement of Oxidative Stress Biomarkers
4.8. Histological Analysis
4.9. Thioflavin S Staining
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Liu, B.; Hong, J.S. Role of microglia in inflammation-mediated neurodegenerative diseases: Mechanisms and strategies for therapeutic intervention. J. Pharmacol. Exp. Ther. 2003, 304, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Amor, S.; Puentes, F.; Baker, D.; van der Valk, P. Inflammation in neurodegenerative diseases. Immunology 2010, 129, 154–169. [Google Scholar] [CrossRef]
- Glass, C.K.; Saijo, K.; Winner, B.; Marchetto, M.C.; Gage, F.H. Mechanisms underlying inflammation in neurodegeneration. Cell 2010, 140, 918–934. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Passamonti, L.; Tsvetanov, K.A.; Jones, P.S.; Bevan-Jones, W.R.; Arnold, R.; Borchert, R.J.; Mak, E.; Su, L.; O’Brien, J.T.; Rowe, J.B. Neuroinflammation and Functional Connectivity in Alzheimer’s Disease: Interactive Influences on Cognitive Performance. J. Neurosci. 2019, 39, 7218–7226. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guzman-Martinez, L.; Maccioni, R.B.; Andrade, V.; Navarrete, L.P.; Pastor, M.G.; Ramos-Escobar, N. Neuroinflammation as a Common Feature of Neurodegenerative Disorders. Front. Pharmacol. 2019, 10, 1008. [Google Scholar] [CrossRef] [Green Version]
- Ransohoff, R.M. How neuroinflammation contributes to neurodegeneration. Science 2016, 353, 777–783. [Google Scholar] [CrossRef] [PubMed]
- Yun, H.S.; Oh, J.; Lim, J.S.; Kim, H.J.; Kim, J.S. Anti-Inflammatory Effect of Wasp Venom in BV-2 Microglial Cells in Comparison with Bee Venom. Insects 2021, 12, 297. [Google Scholar] [CrossRef]
- Abd El-Wahed, A.; Yosri, N.; Sakr, H.H.; Du, M.; Algethami, A.F.M.; Zhao, C.; Abdelazeem, A.H.; Tahir, H.E.; Masry, S.H.D.; Abdel-Daim, M.M.; et al. Wasp Venom Biochemical Components and Their Potential in Biological Applications and Nanotechnological Interventions. Toxins 2021, 13, 206. [Google Scholar] [CrossRef]
- Monteiro, M.C.; Romao, P.R.; Soares, A.M. Pharmacological perspectives of wasp venom. Protein. Pept. Lett. 2009, 16, 944–952. [Google Scholar] [CrossRef]
- Wu, Y.H.; Zhang, Y.; Fang, D.Q.; Chen, J.; Wang, J.A.; Jiang, L.; Lv, Z.F. Characterization of the Composition and Biological Activity of the Venom from Vespa bicolor Fabricius, a Wasp from South China. Toxins 2022, 14, 59. [Google Scholar] [CrossRef]
- Al-Shammery, K.A.; Hozzein, W.N. Antibacterial activities of two potential peptides extracted from Polistes wattii Cameron, 1900 (Vespidae: Polistinae) wasp venom collected at Eastern Province, Saudi Arabia. PLoS ONE 2022, 17, e0264035. [Google Scholar] [CrossRef] [PubMed]
- Baek, H.; Lee, C.J.; Choi, D.B.; Kim, N.S.; Kim, Y.S.; Ye, Y.J.; Kim, Y.S.; Kim, J.S.; Shim, I.; Bae, H. Bee venom phospholipase A2 ameliorates Alzheimer’s disease pathology in Abeta vaccination treatment without inducing neuro-inflammation in a 3xTg-AD mouse model. Sci. Rep. 2018, 8, 17369. [Google Scholar] [CrossRef] [Green Version]
- Ye, M.; Chung, H.S.; Lee, C.; Yoon, M.S.; Yu, A.R.; Kim, J.S.; Hwang, D.S.; Shim, I.; Bae, H. Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer’s disease. J. Neuroinflammation 2016, 13, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vidal, C.; Armisen, M.; Monsalve, R.; Gonzalez-Vidal, T.; Lojo, S.; Lopez-Freire, S.; Mendez, P.; Rodriguez, V.; Romero, L.; Galan, A.; et al. Anaphylaxis to Vespa velutina nigrithorax: Pattern of Sensitization for an Emerging Problem in Western Countries. J. Investig. Allergol. Clin. Immunol. 2021, 31, 228–235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feas, X. Human Fatalities Caused by Hornet, Wasp and Bee Stings in Spain: Epidemiology at State and Sub-State Level from 1999 to 2018. Biology 2021, 10, 73. [Google Scholar] [CrossRef]
- Choi, M.B.; Kim, T.G.; Kwon, O. Recent Trends in Wasp Nest Removal and Hymenoptera Stings in South Korea. J. Med. Entomol. 2019, 56, 254–260. [Google Scholar] [CrossRef] [PubMed]
- Vidal, C. The Asian wasp Vespa velutina nigrithorax: Entomological and allergological characteristics. Clin. Exp. Allergy 2022, 52, 489–498. [Google Scholar] [CrossRef] [PubMed]
- Kinney, J.W.; Bemiller, S.M.; Murtishaw, A.S.; Leisgang, A.M.; Salazar, A.M.; Lamb, B.T. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 2018, 4, 575–590. [Google Scholar] [CrossRef]
- Oakley, H.; Cole, S.L.; Logan, S.; Maus, E.; Shao, P.; Craft, J.; Guillozet-Bongaarts, A.; Ohno, M.; Disterhoft, J.; Van Eldik, L.; et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: Potential factors in amyloid plaque formation. J. Neurosci. 2006, 26, 10129–10140. [Google Scholar] [CrossRef] [Green Version]
- Bilkei-Gorzo, A. Genetic mouse models of brain ageing and Alzheimer’s disease. Pharmacol. Ther. 2014, 142, 244–257. [Google Scholar] [CrossRef]
- Leng, F.; Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nat. Rev. Neurol. 2021, 17, 157–172. [Google Scholar] [CrossRef] [PubMed]
- Morales, I.; Guzman-Martinez, L.; Cerda-Troncoso, C.; Farias, G.A.; Maccioni, R.B. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front. Cell. Neurosci. 2014, 8, 112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pimplikar, S.W. Neuroinflammation in Alzheimer’s disease: From pathogenesis to a therapeutic target. J. Clin. Immunol. 2014, 34, S64–S69. [Google Scholar] [CrossRef] [PubMed]
- Heneka, M.T.; Carson, M.J.; El Khoury, J.; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015, 14, 388–405. [Google Scholar] [CrossRef] [Green Version]
- Lee, J.D.; Park, H.J.; Chae, Y.; Lim, S. An Overview of Bee Venom Acupuncture in the Treatment of Arthritis. Evid. Based Complement. Alternat. Med. 2005, 2, 79–84. [Google Scholar] [CrossRef]
- Gao, Y.; Yu, W.X.; Duan, X.M.; Ni, L.L.; Liu, H.; Zhao, H.R.; Xiao, H.; Zhang, C.G.; Yang, Z.B. Wasp Venom Possesses Potential Therapeutic Effect in Experimental Models of Rheumatoid Arthritis. Evid. Based Complement. Alternat. Med. 2020, 2020, 394625. [Google Scholar] [CrossRef]
- Jiang, T.; Harder, B.; Rojo de la Vega, M.; Wong, P.K.; Chapman, E.; Zhang, D.D. p62 links autophagy and Nrf2 signaling. Free Radic. Biol. Med. 2015, 88, 199–204. [Google Scholar] [CrossRef] [Green Version]
- Le, T.N.; Da Silva, D.; Colas, C.; Darrouzet, E.; Baril, P.; Leseurre, L.; Maunit, B. Asian hornet Vespa velutina nigrithorax venom: Evaluation and identification of the bioactive compound responsible for human keratinocyte protection against oxidative stress. Toxicon 2020, 176, 1–9. [Google Scholar] [CrossRef]
- Jones, L.A.; Sun, E.W.; Martin, A.M.; Keating, D.J. The ever-changing roles of serotonin. Int. J. Biochem. Cell Biol. 2020, 125, 105776. [Google Scholar] [CrossRef]
- Lee, B.H.; Hille, B.; Koh, D.S. Serotonin modulates melatonin synthesis as an autocrine neurotransmitter in the pineal gland. Proc. Natl. Acad. Sci. USA 2021, 118, e2113852118. [Google Scholar] [CrossRef]
- Senechal, Y.; Kelly, P.H.; Dev, K.K. Amyloid precursor protein knockout mice show age-dependent deficits in passive avoidance learning. Behav. Brain Res. 2008, 186, 126–132. [Google Scholar] [CrossRef] [PubMed]
- Ju, S.; Seo, J.Y.; Lee, S.K.; Oh, J.; Kim, J.S. Oral administration of hydrolyzed red ginseng extract improves learning and memory capability of scopolamine-treated C57BL/6J mice via upregulation of Nrf2-mediated antioxidant mechanism. J. Ginseng. Res. 2021, 45, 108–118. [Google Scholar] [CrossRef]
- Kim, S.; Oh, J.; Jang, C.H.; Kim, J.S. Improvement of cognitive function by Gochujang supplemented with tomato paste in a mouse model. Food Sci. Biotechnol. 2019, 28, 1225–1233. [Google Scholar] [CrossRef] [PubMed]
- Seo, J.Y.; Ju, S.H.; Oh, J.; Lee, S.K.; Kim, J.S. Neuroprotective and Cognition-Enhancing Effects of Compound K Isolated from Red Ginseng. J. Agric. Food Chem. 2016, 64, 2855–2864. [Google Scholar] [CrossRef]
- Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248–254. [Google Scholar] [CrossRef] [PubMed]
- Kruger, N.J. The Bradford method for protein quantitation. Methods Mol. Biol. 1994, 32, 9–15. [Google Scholar] [PubMed]
Group | Experimental Groups (n = 7 per Group) | |||||
---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | |
Mouse type | WT (C57BL/6J) | 5xFAD Tg | ||||
Sample treatment (i.p.) | Vehicle | Vehicle | DONE | BV | WV | |
- | - | 5 mg/kg BW/day | 25 μg/kg BW/day | 250 μg/kg BW/day | 400 μg/kg BW/day |
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Jeong, Y.A.; Yun, H.S.; Kim, Y.; Jang, C.H.; Lim, J.S.; Kim, H.J.; Choi, M.B.; Jung, J.W.; Oh, J.; Kim, J.-S. Long-Term Administration of Vespa velutina nigrithorax Venom Ameliorates Alzheimer’s Phenotypes in 5xFAD Transgenic Mice. Toxins 2023, 15, 203. https://doi.org/10.3390/toxins15030203
Jeong YA, Yun HS, Kim Y, Jang CH, Lim JS, Kim HJ, Choi MB, Jung JW, Oh J, Kim J-S. Long-Term Administration of Vespa velutina nigrithorax Venom Ameliorates Alzheimer’s Phenotypes in 5xFAD Transgenic Mice. Toxins. 2023; 15(3):203. https://doi.org/10.3390/toxins15030203
Chicago/Turabian StyleJeong, Yoon Ah, Hyun Seok Yun, Yoonsu Kim, Chan Ho Jang, Ji Sun Lim, Hyo Jung Kim, Moon Bo Choi, Jae Woo Jung, Jisun Oh, and Jong-Sang Kim. 2023. "Long-Term Administration of Vespa velutina nigrithorax Venom Ameliorates Alzheimer’s Phenotypes in 5xFAD Transgenic Mice" Toxins 15, no. 3: 203. https://doi.org/10.3390/toxins15030203