Kefir recovered depressive-like behaviour in CantonS lineage of Drosophila melanogaster exposed to chronic unpredictable mild stress protocol
In: Beneficial MicrobesCellular and Structural Biology Program, Institute of Biology, State University of Campinas, UNICAMP, São Paulo, Brazil
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Abstract
Chronic unpredictable mild stress (CUMS) is a widely accepted method for inducing depressive-like states in animal models. We decided to explore the effects of CUMS on the CantonS lineage of Drosophila melanogaster, which differs from the OregonR lineage in various ways. Additionally, we wanted to investigate the potential benefits of kefir in treating these chronically stressed flies, as previous research has shown promising results in using kefir components for depression treatment. To begin, we exposed male CantonS flies to a 10-day CUMS protocol and compared them to non-stressed flies. Within the stressed group, we had two subgroups: one treated with kefir (CUMS + Kefir group) and the other treated with sertraline (positive control). We then analysed various factors including serotonin levels, brain structure, markers of oxidative damage in lipids and proteins, and behavioural manifestations such as sociability, locomotor function, and anhedonic-like behaviour. Our results showed that flies exposed to CUMS experienced a decrease in serotonin levels without any signs of degeneration. They also exhibited reduced sociability, increased motor agitation, and decreased sucrose consumption, which are all indicative of stress-induced depressive-like behaviour. However, treatment with sertraline partially reversed these effects. Interestingly, treatment with kefir not only restored serotonin levels but also improved sociability and anhedonic-like behaviours. Additionally, flies in the CUMS + Kefir group had a longer lifespan compared to their untreated counterparts. These findings suggest that kefir has multiple advantageous effects on flies subjected to the 10-day CUMS protocol. In conclusion, our study demonstrates that the CantonS lineage of D. melanogaster displays depressive-like manifestations after exposure to CUMS. Furthermore, kefir emerges as a powerful nutritional tool capable of reversing these effects and promoting beneficial outcomes in chronically stressed flies.
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Aguglia, E., Casacchia, M., Cassano, G.B., Faravelli, C., Ferrari, G., Giordano, P., Pancheri, P., Ravizza, L., Trambuchi, M. and Bolino, F., 1993. Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. International Clinical Psychopharmacology 8: 197-202. https://doi.org/10.1097/00004850-199300830-00010
-
Alqurashi, G.K., Hindi, E.A., Zayed, M.A., Abd El-Aziz, G.S., Alturkistani, H.A., Ibrahim, R.F., Al-Thepyani, M.A., Bakhlgi, R., Alzahrani, N.A., Ashraf, G.M. and Alghamdi, B.S., 2022. The impact of chronic unpredictable mild stress-induced depression on spatial, recognition and reference memory tasks in mice: behavioral and histological study. Behavioral Sciences 12: 166. https://doi.org/10.3390/bs12060166
-
Antoniuk, S., Bijata, M., Ponimaskin, E. and Wlodarczyk, J., 2019. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neuroscience Biobehavioral Reviews 99: 101-116. https://doi.org/10.1016/j.neubiorev.2018.12.002
-
Araujo, S.M., Bortolotto, V.C., Poetini, M.R., Dahleh, M.M.M., Couto, S.F., Pinheiro, F.C., Meichtry, L.B., Musachio, E.A.S., Ramborger, B.P., Roehrs, R., Guerra, G.P. and Prigol, M., 2021. γ-Oryzanol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in a chronic unpredictable mild stress model of depression in Drosophila melanogaster. Stress 24: 282-293. https://doi.org/10.1080/10253890.2020.1790519
-
Araujo, S.M., Poetini, M.R., Bortolotto, V.C., de Freitas-Couto, S., Pinheiro, F.C., Meichtry, L.B., de Almeida, F.P., Santos-Musachio, E.A., de Paula, M.T. and Prigol, M., 2018. Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster. Behavioral Brain Research 351: 104-113. https://doi.org/10.1016/j.bbr.2018.05.016
-
Azizi, N.F., Kumar, M.R., Yeap, S.K., Abdullah, J.O., Khalid, M., Omar, A.R., Osman, M.A., Mortadza, S.A.S. and Alitheen, N.B., 2021. Kefir and its biological activities. Foods 10: 1210. https://doi.org/10.3390/foods10061210
-
Bastiaanssen, T.F.S., Cussotto, S., Claesson, M.J., Clarke, G., Dinan, T.G. and Cryan, J.F., 2020. Gutted! Unraveling the role of the microbiome in major depressive disorder. Harvard Review of Psychiatry 28: 26-39. https://doi.org/10.1097/HRP.0000000000000243
-
Batista, L.L., Malta, S.M., Guerra-Silva, H.C., Borges, L.D.F., Rocha, L.O., da Silva, J.R., Rodrigues, T.S., Venturini, G., Padilha, K., da Costa-Pereira, A., Espindola, F.S. and Ueira-Vieira, C., 2021. Kefir metabolites in a fly model for Alzheimer’s disease. Scientific Reports 11: 11262. https://doi.org/10.1038/s41598-021-90749-8
-
Becker, M., Pinhasov, A. and Ornoy, A., 2021. Animal models of depression: what can they teach us about the human disease? Diagnostics 11: 123. https://doi.org/10.3390/diagnostics11010123
-
Billeter, J.C., Jagadeesh, S., Stepek, N., Azanchi, R. and Levine, J.D., 2012. Drosophila melanogaster females change mating behaviour and offspring production based on social context. Proceedings of the Royal Society B 279: 2417-2425. https://doi.org/10.1098/rspb.2011.2676
-
Borrelli, L., Aceto, S., Agnisola, C., De Paolo, S., Dipineto, L., Stilling, R.M., Dinan, T.G., Cryan, J.F., Menna, L.F. and Alessandro-Fioretti, A., 2016. Probiotic modulation of the microbiota-gut-brain axis and behaviour in zebrafish. Scientific Reports 6: 30046. https://doi.org/10.1038/srep30046
-
Capuco, A., Urits, I., Hasoon, J., Chun, R., Gerald, B., Wang, J.K., Kassem, H., Ngo, A.L., Abd-Elsayed, A., Simopoulos, T., Kaye, A.D. and Viswanath, O., 2020. Current perspectives on gut microbiome dysbiosis and depression. Advances in Therapy 37: 1328-1346. https://doi.org/10.1007/s12325-020-01272-7
-
Diegelmann, S., Jansen, A., Jois, S., Kastenholz, K., Velo-Escarcena, L., Strudthoff, N. and Scholz, H., 2017. The CApillary FEeder assay measures food intake in Drosophila melanogaster. Journal of Visualized Experiments 121: e55024. https://doi.org/10.3791/55024
-
Dragioti, E., Solmi, M., Favaro, A., Fusar-Poli, P., Dazzan, P., Thompson, T., Stubbs, B., Firth, J., Fornaro, M., Tsartsalis, D., Carvalho, A.F., Vieta, E., McGuire, P., Young, A.H., Shin, J.I., Correll, C.U. and Evangelou, E., 2019. Association of antidepressant use with adverse health outcomes: a systematic umbrella review. JAMA Psychiatry 76: 1241-1255. https://doi.org/10.1001/jamapsychiatry.2019.2859
-
Dukas, R., 2020. Natural history of social and sexual behavior in fruit flies. Scientific Reports 10: 21932. https://doi.org/10.1038/s41598-020-79075-7
-
Eleftherianos, I., More, K., Spivack, S., Paulin, E., Khojandi, A. and Shukla, S., 2014. Nitric oxide levels regulate the immune response of Drosophila melanogaster reference laboratory strains to bacterial infections. Infection and Immunity 82: 4169-4181. https://doi.org/10.1128/IAI.02318-14
-
Enell, L., Hamasaka, Y., Kolodziejczyk, A. and Nässel, D.R., 2007. Gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter. Journal of Comparative Neurology 505: 18-31. https://doi.org/10.1002/cne.21472
-
Farag, M.A., Jomaa, S.A., El-Wahed, A.A. and El-Seedi, A.H.R., 2020. The many faces of kefir fermented dairy products: quality characteristics, flavour chemistry, nutritional value, health benefits, and safety. Nutrients 12: 346. https://doi.org/10.3390/nu12020346
-
Feinerman, O., 2021. Animal behavior: Drosophila melanogaster goes social. Current Biology 31: R138-R140. https://doi.org/10.1016/j.cub.2020.11.047
-
Fogaça, M.V. and Duman, R.S., 2019. Cortical GABAergic dysfunction in stress and depression: new insights for therapeutic interventions. Frontiers in Cellular Neuroscience 13: 87. https://doi.org/10.3389/fncel.2019.00087
-
Gargano, J.W., Martin, I., Bhandari, P. and Grotewiel, M.S., 2005. Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila. Experimental Gerontology 40: 386-395. https://doi.org/10.1016/j.exger.2005.02.005
-
Groen, C.M., Podratz, J.L., Treb, K. and Windeban, A.J.K., 2018. Drosophila strain specific response to cisplatin neurotoxicity. Fly 12: 174-182. https://doi.org/10.1080/19336934.2019.1565257
-
Gürbüzel, M., Oral, E., Kizilet, H., Halici, Z. and Gulec, M., 2012. Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster. Mutation Research 748: 17-20. https://doi.org/10.1016/j.mrgentox.2012.06.004
-
Haddadi, M., Jahromi, S.R., Sagar, B.K., Patil, R.K., Shivanandappa, T. and Ramesh, S.R., 2014. Brain aging, memory impairment and oxidative stress: a study in Drosophila melanogaster. Behavioral Brain Research 259: 60-69. https://doi.org/10.1016/j.bbr.2013.10.036
-
Hair, J.F., Black, W.L., Babin, B.J., Anderson, R.E. and Tatham, R.L., 2009. Análise multivariada de dados. 6th ed. Bookman, Porto Alegre, RS, Brasil.
-
Hermanns, T., Graf-Boxhorn, S., Poek, B. and Strauss, R., 2022. Octopamine mediates sugar relief from a chronic-stress-induced depression-like state in Drosophila. Current Biology 32: 4048-4056.e3. https://doi.org/10.1016/j.cub.2022.07.016
-
Jajoo, A., Donlon, C., Shnayder, S., Levin, M. and McVey, M., 2020. Sertraline induces DNA damage and cellular toxicity in Drosophila that can be ameliorated by antioxidants. Scientific Reports 10: 4512. https://doi.org/10.1038/s41598-020-61362-y
-
Karakula-Juchnowicz, H., Rog, J., Juchnowicz, D., Łoniewski, I., Skonieczna-Żydecka, K., Krukow, P., Futyma-Jedrzejewska, M. and Kaczmarczyk, M., 2019. The study evaluating the effect of probiotic supplementation on the mental status, inflammation, and intestinal barrier in major depressive disorder patients using gluten-free or gluten-containing diet (SANGUT study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol. Nutrition Journal 18: 50. https://doi.org/10.1186/s12937-019-0475-x
-
Kazemi, A., Noorbala, A.A., Azam, K., Eskandari, M.H. and Djafarian, K., 2019. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clinical Nutrition 38: 522-528. https://doi.org/10.1016/j.clnu.2018.04.010
-
Kverno, K.S. and Mangano, E., 2021. Treatment-resistant depression: approaches to treatment. Journal of Psychosocial Nursing and Mental Health Service 59: 7-11. https://doi.org/0.3928/02793695-20210816-01
-
Malacrida, S., De Lazzari, F., Mrakic-Sposta, S., Vezzoli, A., Zordan, M.A., Bisaglia, M., Menti, G.M., Meda, N., Frighetto, G., Bosco, G., Dal Cappello, T., Strapazzon, G., Reggiani, C., Gussoni, M. and Megighian, A., 2022. Lifespan and ROS levels in different Drosophila melanogaster strains after 24 h hypoxia exposure. Biology Open 11: bio059386. https://doi.org/10.1242/bio.059386
-
Malta, S.M., Batista, L.L., Silva, H.C.G., Franco, R.R., Silva, M.H., Rodrigues, T.S., Correia, L.I.V., Martins, M.M., Venturini, G., Espindola, F.S., da Silva, M.V. and Ueira-Vieira, C., 2022. Identification of bioactive peptides from a Brazilian kefir sample, and their anti-Alzheimer potential in Drosophila melanogaster. Scientific Reports 12: 11065. https://doi.org/10.1038/s41598-022-15297-1
-
Markov, D.D. and Novosadova, E.V., 2022. Chronic unpredictable mild stress model of depression: possible sources of poor reproducibility and latent variables. Biology 11: 1621. https://doi.org/10.3390/biology11111621
-
Mayneris-Perxachs, J., Castells-Nobau, A., Arnoriaga-Rodrı́guez, M., Martin, M., Vega-Correa, L., Zapata, C., Burokas, A., Blasco, G., Coll, C., Escrichs, A., Biarnés, C., Moreno-Navarrete, J.M., Puig, J., Garre-Olmo, J., Ramos, R., Pedraza, S., Brugada, R., Vilanova, J.C., Serena, J., Gich, J., Ramió-Torrentà, L., Pérez-Brocal, V., Moya, A., Pamplona, R., Sol, J., Jové, M., Ricart, W., Portero-Otin, M., Deco, G., Maldonado, R. and Fernández-Real, J.M., 2022. Microbiota alterations in proline metabolism impact depression. Cell Metabolism 34: 681-701. https://doi.org/10.1016/j.cmet.2022.04.001
-
Meichtry, L.B., Poetini, M.R., Dahleh, M.M.M., Araujo, S.M., Musachio, E.A.S., Bortolotto, V.C., de Freitas-Couto, S., Somacal, S., Emanuelli, T., Gayer, M.C., Roehrs, R., Guerra, G.P. and Prigol, M., 2020. Addition of saturated and trans-fatty acids to the diet induces depressive and anxiety-like behaviors in Drosophila melanogaster. Neuroscience 443: 164-175. https://doi.org/10.1016/j.neuroscience.2020.07.042
-
Mendes-Silva, A.P., Fujimura, P.T., Silva, J.R.D.C., Teixeira, A.L., Vieira, E.M., Guedes, P.H.G., Barroso, L.S.S., Nicolau, M.S., Ferreira, J.D.R., Bertola, L., Nicolau, E.S., Tolentino-Araújo, G.T., Berlezzi, C.M.S.F., Rodrigues, T.S., Borges, L.D.F., Gomes, M.S., Amaral, L.R.D., Bonetti, A.M., Ueira-Vieira, C. and Diniz, B.S., 2019. Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study. Journal of Psychiatry Research 111: 110-120. https://doi.org/10.1016/j.jpsychires.2019.01.019
-
Mendes-Silva, A.P., Prevot, T.D., Banasr, M., Sibille, E. and Diniz, B.S., 2022. Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress. Frontiers in Cellular Neuroscience 16: 999303. https://doi.org/10.3389/fncel.2022.999303
-
Morgan, S.L., Seggio, J.A., Nascimento, N.F., Huh, D.D., Hicks, J.A., Sharp, K.A., Axelrod, J.D. and Wang, K.C., 2016. The phenotypic effects of royal jelly on wild-type D. melanogaster are strain-specific. PLoS ONE 11: e0159456. https://doi.org/10.1371/journal.pone.0159456
-
Neckameyer, W.S. and Nieto-Romero, A.R., 2015. Response to stress in Drosophila is mediated by gender, age and stress paradigm. Stress 18: 254-266. https://doi.org/10.3109/10253890.2015.1017465
-
Nollet, M., 2021. Models of depression: unpredictable chronic mild stress in mice. Current Protocols 1: e208. https://doi.org/10.1002/cpz1.208
-
Peirce, J.M. and Alviña, K., 2019. The role of inflammation and the gut microbiome in depression and anxiety. Journal of Neuroscience Research 10: 1223-1241. https://doi.org/10.1002/jnr.24476
-
Peluzio, M.D.C.G., Dias, M.M.E., Martinez, J.A. and Milagro, F.I., 2021. Kefir and intestinal microbiota modulation: implications in human health. Frontiers in Nutrition 8: 638740. https://doi.org/10.3389/fnut.2021.638740
-
Perez-Caballero, L., Torres-Sanchez, S., Romero-López-Alberca, C., González-Saiz, F., Mico, J.A. and Berrocoso, E., 2019. Monoaminergic system and depression. Cell and Tissue Research 377: 107-113. https://doi.org/10.1007/s00441-018-2978-8
-
Ries, A.S., Hermanns, T., Poeck, B. and Strauss, S., 2017. Serotonin modulates a depression-like state in Drosophila responsive to lithium treatment. Nature Communications 8: 15738. https://doi.org/10.1038/ncomms15738
-
Rooke, R., Rasool, A., Schneider, J. and Levine, J.D., 2020. Drosophila melanogaster behaviour changes in different social environments based on group size and density. Communications Biology 3: 304. https://doi.org/10.1038/s42003-020-1024-z
-
Sechter, D., Troy, S., Paternetti, S. and Boyer, P., 1999. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. European Psychiatry 14: 41-48. https://doi.org/10.1016/s0924-9338(99)80714-7
-
Simon, A.F., Chou, M.T., Salazar, E.D., Nicholson, T., Saini, N., Metchev, S. and Krantz, D.E., 2012. A simple assay to study social behavior in Drosophila: measurement of social space within a group. Gene, Brain and Behavior 11: 243-252. https://doi.org/10.1111/j.1601-183X.2011.00740.x
-
Soltanmoradi, H., Maniati, M.S., Davoodabadi, A., Mosapour, A., Samavarchi-Tehrani, S., Pazhoohan, M., Daemi, F. and Khaleghzadeh-Ahangar, H., 2021. A probiotic supplement, Lactobacillus rhamnosus GG, and kefir separately can improve mood and exhibit potential anti-depressant-like activities in mice. Acta Alimentaria 50: 393-403. https://doi.org/10.1556/066.2021.00021
-
Sonali, S., Ray, B., Tousif, H.A., Rathipriya, A.G., Sunanda, T., Mahalakshmi, A.M., Rungratanawanich, W., Essa, M.M., Qoronfleh, M.W., Chidambaram, S.B. and Song, B.J., 2022. Mechanistic insights into the link between gut dysbiosis and major depression: an extensive review. Cells 11: 1362. https://doi.org/10.3390/cells11081362
-
Van de Wouw, M., Walsh, A.M., Crispie, F., van Leuven, L., Lyte, J.M., Boehme, M., Clarke, G., Dinan, T.G., Cotter, P.D. and Cryan, J.F., 2020. Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse. Microbiome 8: 67. https://doi.org/10.1186/s40168-020-00846-5
-
Yang, Z., Bertolucci, F., Wolf, R. and Heinsenberg, M., 2013. Flies cope with uncontrollable stress by learned helplessness. Current Biology 23: 799-803. https://doi.org/10.1016/j.cub.2013.03.054
-
Yost, R.T., Robinson, J.W., Baxter, C.M., Scott, A.M., Brown, L.P., Aletta, M.S., Hakimjavadi, R., Lone, A., Cumming, R.C., Dukas, R., Mozer, B. and Simon, A.F., 2020. Abnormal social interactions in Drosophila mutant of an autism candidate gene: neuroligin 3. International Journal of Molecular Sciences 21: 4601. https://doi.org/10.3390/ijms21134601
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Kefir recovered depressive-like behaviour in CantonS lineage of Drosophila melanogaster exposed to chronic unpredictable mild stress protocol
In: Beneficial MicrobesCellular and Structural Biology Program, Institute of Biology, State University of Campinas, UNICAMP, São Paulo, Brazil
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Abstract
Chronic unpredictable mild stress (CUMS) is a widely accepted method for inducing depressive-like states in animal models. We decided to explore the effects of CUMS on the CantonS lineage of Drosophila melanogaster, which differs from the OregonR lineage in various ways. Additionally, we wanted to investigate the potential benefits of kefir in treating these chronically stressed flies, as previous research has shown promising results in using kefir components for depression treatment. To begin, we exposed male CantonS flies to a 10-day CUMS protocol and compared them to non-stressed flies. Within the stressed group, we had two subgroups: one treated with kefir (CUMS + Kefir group) and the other treated with sertraline (positive control). We then analysed various factors including serotonin levels, brain structure, markers of oxidative damage in lipids and proteins, and behavioural manifestations such as sociability, locomotor function, and anhedonic-like behaviour. Our results showed that flies exposed to CUMS experienced a decrease in serotonin levels without any signs of degeneration. They also exhibited reduced sociability, increased motor agitation, and decreased sucrose consumption, which are all indicative of stress-induced depressive-like behaviour. However, treatment with sertraline partially reversed these effects. Interestingly, treatment with kefir not only restored serotonin levels but also improved sociability and anhedonic-like behaviours. Additionally, flies in the CUMS + Kefir group had a longer lifespan compared to their untreated counterparts. These findings suggest that kefir has multiple advantageous effects on flies subjected to the 10-day CUMS protocol. In conclusion, our study demonstrates that the CantonS lineage of D. melanogaster displays depressive-like manifestations after exposure to CUMS. Furthermore, kefir emerges as a powerful nutritional tool capable of reversing these effects and promoting beneficial outcomes in chronically stressed flies.
| All Time | Past 365 days | Past 30 Days | |
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| Abstract Views | 1388 | 341 | 27 |
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| PDF Views & Downloads | 80 | 6 | 0 |
