Modelaje de funciones neurocognitivas en roedores: dos paradigmas de memoria dependiente del hipocampo y del contexto histórico-científico de los modelos animales en neurociencias
DOI:
https://doi.org/10.22544/rcps.v44i01.09Palabras clave:
memoria declarativa, hipocampo, modelos animalesResumen
Históricamente, las neurociencias iniciaron con estudios conductuales y observacionales en seres humanos. Posteriormente, le siguieron estudios clínicos en pacientes con daños neurológicos y, más tarde, las imágenes médicas del cerebro aportaron evidencia para entender los mecanismos neurobiológicos subyacentes a la conducta y funciones cognitivas. Sin embargo, mucho del progreso de las neurociencias se ha basado en modelos animales. Este trabajo detalla los contextos histórico y científico que llevaron al desarrollo de algunos modelos animales dentro del ámbito de las neurociencias, y ejemplifica la utilidad y robustez de esta herramienta de investigación mediante la visualización de dos paradigmas utilizados para evaluar una misma función neurocognitiva. Con este fin, se reportan los resultados de la estandarización de dos modelos de memoria espacial dependiente del hipocampo, utilizando dos especies de roedores: el laberinto de Barnes, estandarizado con ratas Wistar, y el laberinto acuático de Morris, utilizando ratones C57bl/6. En ambos paradigmas se demuestra que la escopolamina, un potente agente anticolinérgico que bloquea los receptores muscarínicos en el hipocampo, disrumpe la capacidad de ambas especies de roedores para memorizar la localización del punto de escape de los respectivos laberintos. Al igual que los muchos modelos animales utilizados en diversas áreas de las ciencias biomédicas, estos sencillos pero robustos paradigmas de las neurociencias se estandarizaron como una plataforma para la futura exploración de potenciales terapias farmacológicas; en este caso, el descubrimiento de posibles fármacos neuroprotectores contra disfunciones cognitivas asociadas al hipocampo, en particular, demencias como la enfermedad de Alzheimer.Citas
Akpan, B. (2020). Classical and Operant Conditioning—Ivan Pavlov; Burrhus Skinner (pp. 71-84). Springer, Cham. https://doi.org/10.1007/978-3-030-43620-9_6
Amaral, D. G., Augustinack, J., Barbas, H., Frosch, M., Gabrieli, J., Luebke, J., Rakic, P., Rosene, D., & Rushmore, R. J. (2024). The analysis of H.M.’s brain: A brief review of status and plans for future studies and tissue archive. Hippocampus, 34(2), 52-57. https://doi.org/10.1002/HIPO.23597
Arsalidou, M., & Taylor, M. J. (2011). Is 2+2=4? Meta-analyses of brain areas needed for numbers and calculations. NeuroImage, 54(3), 2382-2393. https://doi.org/10.1016/j.neuroimage.2010.10.009
Attar, A., Liu, T., Chan, W.-T. C., Hayes, J., Nejad, M., Lei, K., & Bitan, G. (2013). A Shortened Barnes Maze Protocol Reveals Memory Deficits at 4-Months of Age in the Triple-Transgenic Mouse Model of Alzheimer’s Disease. PLoS ONE, 8(11), e80355. https://doi.org/10.1371/journal.pone.0080355
Banerjee, R., Rai, A., Iyer, S. M., Narwal, S., & Tare, M. (2022). Animal models in the study of Alzheimer’s disease and Parkinson’s disease: A historical perspective. Animal Models and Experimental Medicine, 5(1), 27-37. https://doi.org/10.1002/ame2.12209
Baro, F., & Priftis, K. (2023). Islands of memory in Henry Molaison and other patients with global episodic amnesia: A mini review. OSFPREPRINTS. https://doi.org/10.31219/OSF.IO/QAJ4S
Bauman, M. D., & Schumann, C. M. (2018). Advances in nonhuman primate models of autism: Integrating neuroscience and behavior. Experimental Neurology, 299(Pt A), 252-265. https://doi.org/10.1016/J.EXPNEUROL.2017.07.021
Bear, M. F. (2020). Neuroscience: exploring the brain (B. W. Connors & M. A. Paradiso, Eds.; Enhanced fourth e...) [Book]. Jones & Bartlett Learning.
Bejar, C., Wang, R. H., & Weinstock, M. (1999). Effect of rivastigmine on scopolamine-induced memory impairment in rats. European Journal of Pharmacology, 383(3), 231-240. https://doi.org/10.1016/S0014-2999(99)00643-3
Bertrand, D., & Wallace, T. L. (2020). A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders. In M. Shoaib & T. L. Wallace (Eds.), Behavioral Pharmacology of the Cholinergic System (pp. 1-28). Springer International Publishing. https://doi.org/10.1007/7854_2020_141
Bhuvanendran, S., Kumari, Y., Othman, I., & Shaikh, M. F. (2018). Amelioration of Cognitive Deficit by Embelin in a Scopolamine-Induced Alzheimer’s Disease-Like Condition in a Rat Model. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00665
Charité – Universitätsmedizin Berlin. (2022). Animal Research 2022. https://Charite3r.Charite.de/En/Animal_research/Animal_research/Animal_research_2022/
Coupland, C. A. C., Hill, T., Dening, T., Morriss, R., Moore, M., & Hippisley-Cox, J. (2019). Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Internal Medicine, 179(8), 1084. https://doi.org/10.1001/JAMAINTERNMED.2019.0677
Curdt, N., Schmitt, F. W., Bouter, C., Iseni, T., Weile, H. C., Altunok, B., Beindorff, N., Bayer, T. A., Cooke, M. B., & Bouter, Y. (2022). Search strategy analysis of Tg4-42 Alzheimer Mice in the Morris Water Maze reveals early spatial navigation deficits. Scientific Reports, 12(1), 1-14. https://doi.org/10.1038/s41598-022-09270-1
Curtis, H. J., & Cole, K. S. (1940). Membrane action potentials from the squid giant axon. Journal of Cellular and Comparative Physiology, 15(2), 147-157.
Dannenberg, H., Young, K., & Hasselmo, M. (2017). Modulation of hippocampal circuits by muscarinic and nicotinic receptors. Frontiers in Neural Circuits, 11, 315341. https://doi.org/10.3389/FNCIR.2017.00102/BIBTEX
de Sousa Fernandes, M. S., Ordônio, T. F., Santos, G. C. J., Santos, L. E. R., Calazans, C. T., Gomes, D. A., & Santos, T. M. (2020). Effects of Physical Exercise on Neuroplasticity and Brain Function: A Systematic Review in Human and Animal Studies. Neural Plasticity, 2020, 1-21. https://doi.org/10.1155/2020/8856621
Deisseroth, K., Feng, G., Majewska, A. K., Miesenböck, G., Ting, A., & Schnitzer, M. J. (2006). Next-generation optical technologies for illuminating genetically targeted brain circuits. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 26(41), 10380-10386. https://doi.org/10.1523/JNEUROSCI.3863-06.2006
D’Hooge, R., & De Deyn, P. P. (2001). Applications of the Morris water maze in the study of learning and memory. Brain Research Reviews, 36(1), 60-90. https://doi.org/10.1016/S0165-0173(01)00067-4
Edwards, S. R., Hamlin, A. S., Marks, N., Coulson, E. J., & Smith, M. T. (2014). Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer’s disease. Clinical and Experimental Pharmacology & Physiology, 41(10), 798-806. https://doi.org/10.1111/1440-1681.12277
Eldefrawi, M. E., Britten, A. G., & Eldefrawi, A. T. (1971). Acetylcholine Binding to Torpedo Electroplax: Relationship to Acetylcholine Receptors. Science, 173(3994), 338-340. https://doi.org/10.1126/SCIENCE.173.3994.338
Eldefrawi, M. E., & Eldefrawi, A. T. (1972). Characterization and Partial Purification of the Acetylcholine Receptor from Torpedo Electroplax. Proceedings of the National Academy of Sciences, 69(7), 1776-1780. https://doi.org/10.1073/PNAS.69.7.1776
Eskildsen, S. F., Coupé, P., Fonov, V. S., Pruessner, J. C., & Collins, D. L. (2015). Structural imaging biomarkers of Alzheimer’s disease: predicting disease progression. Neurobiology of Aging, 36 Suppl 1(S1), S23-S31. https://doi.org/10.1016/J.NEUROBIOLAGING.2014.04.034
Etkin, A., & Wager, T. D. (2007). Functional Neuroimaging of Anxiety: A Meta-Analysis of Emotional Processing in PTSD, Social Anxiety Disorder, and Specific Phobia. The American Journal of Psychiatry, 164(10), 1476-1488. https://doi.org/10.1176/APPI.AJP.2007.07030504
Fernández de Sevilla, D., Núñez, A., & Buño, W. (2021). Muscarinic Receptors, from Synaptic Plasticity to its Role in Network Activity. Neuroscience, 456, 60-70. https://doi.org/10.1016/J.NEUROSCIENCE.2020.04.005
Gawel, K., Gibula, E., Marszalek-Grabska, M., Filarowska, J., & Kotlinska, J. H. (2019). Assessment of spatial learning and memory in the Barnes maze task in rodents—methodological consideration. Naunyn-Schmiedeberg’s Archives of Pharmacology, 392(1), 1-18. https://doi.org/10.1007/s00210-018-1589-y
Gulyás, M., Bencsik, N., Pusztai, S., Liliom, H., & Schlett, K. (2016). AnimalTracker: An ImageJ-Based Tracking API to Create a Customized Behaviour Analyser Program. Neuroinformatics, 14(4), 479-481. https://doi.org/10.1007/S12021-016-9303-Z/FIGURES/1
Heimer-McGinn, V. R., Wise, T. B., Hemmer, B. M., Dayaw, J. N. T., & Templer, V. L. (2020). Social housing enhances acquisition of task set independently of environmental enrichment: A longitudinal study in the Barnes maze. Learning & Behavior, 48(3), 322-334. https://doi.org/10.3758/S13420-020-00418-5
Istifo, N. N., AL- Zobaidy, M. A., & Abass, K. S. (2024). Long-Term Effects of Scopolamine on Brain Tissue of Mice. Journal of the Faculty of Medicine Baghdad, 66(3), 320-328. https://doi.org/10.32007/jfacmedbaghdad.6632323
Kempermann, G., Song, H., & Gage, F. H. (2015). Neurogenesis in the Adult Hippocampus. Cold Spring Harbor Perspectives in Biology, 7(9), a018812. https://doi.org/10.1101/CSHPERSPECT.A018812
Laczó, J., Markova, H., Lobellova, V., Gazova, I., Parizkova, M., Cerman, J., Nekovarova, T., Vales, K., Klovrzova, S., Harrison, J., Windisch, M., Vlcek, K., Svoboda, J., Hort, J., & Stuchlik, A. (2017a). Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans. Psychopharmacology, 234(4), 535-547. https://doi.org/10.1007/S00213-016-4488-2
Laczó, J., Markova, H., Lobellova, V., Gazova, I., Parizkova, M., Cerman, J., Nekovarova, T., Vales, K., Klovrzova, S., Harrison, J., Windisch, M., Vlcek, K., Svoboda, J., Hort, J., & Stuchlik, A. (2017b). Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans. Psychopharmacology, 234(4), 535-547. https://doi.org/10.1007/S00213-016-4488-2
Litwińczuk, M. C., Trujillo-Barreto, N., Muhlert, N., Cloutman, L., & Woollams, A. (2023). Relating Cognition to both Brain Structure and Function: A Systematic Review of Methods. Brain Connectivity, 13(3), 120-132. https://doi.org/10.1089/BRAIN.2022.0036
Maguire, E. A., Gadian, D. G., Johnsrude, I. S., Good, C. D., Ashburner, J., Frackowiak, R. S. J., & Frith, C. D. (2000). Navigation-related structural change in the hippocampi of taxi drivers. Proceedings of the National Academy of Sciences of the United States of America, 97(8), 4398-4403. https://doi.org/10.1073/pnas.070039597
Maguire, E. A., Woollett, K., & Spiers, H. J. (2006). London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis. Hippocampus, 16(12), 1091-1101. https://doi.org/10.1002/HIPO.20233
Malikowska-Racia, N., Podkowa, A., & Sałat, K. (2018). Phencyclidine and Scopolamine for Modeling Amnesia in Rodents: Direct Comparison with the Use of Barnes Maze Test and Contextual Fear Conditioning Test in Mice. Neurotoxicity Research, 34(3), 431-441. https://doi.org/10.1007/S12640-018-9901-7
Mauguière, F., & Corkin, S. (2015). H.M. never again! An analysis of H.M.’s epilepsy and treatment. Revue Neurologique, 171(3), 273-281. https://doi.org/10.1016/j.neurol.2015.01.002
Miller, G. (2006). Optogenetics. Shining new light on neural circuits. Science (New York, N.Y.), 314(5806), 1674-1676. https://doi.org/10.1126/SCIENCE.314.5806.1674
Minkeviciene, R., Banerjee, P., & Tanila, H. (2004). Memantine Improves Spatial Learning in a Transgenic Mouse Model of Alzheimer’s Disease. Journal of Pharmacology and Experimental Therapeutics, 311(2), 677-682. https://doi.org/10.1124/jpet.104.071027
Moreno-Jiménez, E. P., Terreros-Roncal, J., Flor-García, M., Rábano, A., & Llorens-Martín, M. (2021). Evidences for Adult Hippocampal Neurogenesis in Humans. Journal of Neuroscience, 41(12), 2541-2553. https://doi.org/10.1523/JNEUROSCI.0675-20.2020
Pattanayak, R., Sagar, R., & Shah, B. (2014). The study of patient henry Molaison and what it taught us over past 50 years: Contributions to neuroscience. Journal of Mental Health and Human Behaviour, 19(2), 91-93. https://doi.org/10.4103/0971-8990.153719
Planchez, B., Surget, A., & Belzung, C. (2019). Animal models of major depression: drawbacks and challenges. Journal of Neural Transmission 2019 126:11, 126(11), 1383-1408. https://doi.org/10.1007/S00702-019-02084-Y
Qiao, N., Ma, L., Zhang, Y., & Wang, L. (2023). Update on Nonhuman Primate Models of Brain Disease and Related Research Tools. Biomedicines, 11(9), 2516. https://doi.org/10.3390/biomedicines11092516
Rao, Y. L., Ganaraja, B., Murlimanju, B. V., Joy, T., Krishnamurthy, A., & Agrawal, A. (2022). Hippocampus and its involvement in Alzheimer’s disease: a review. 3 Biotech, 12(2), 1-10. https://doi.org/10.1007/S13205-022-03123-4/FIGURES/2
Riedel, G., Kang, S. H., Choi, D. Y., & Platt, B. (2009). Scopolamine-induced deficits in social memory in mice: Reversal by donepezil. Behavioural Brain Research, 204(1), 217-225. https://doi.org/10.1016/j.bbr.2009.06.012
Rodríguez, L., Scheuber, M. I., Shan, H., Braun, M., & Schwab, M. E. (2024). Barnes maze test for spatial memory: A new, sensitive scoring system for mouse search strategies. Behavioural Brain Research, 458, 114730. https://doi.org/10.1016/j.bbr.2023.114730
Rost, B. R., Wietek, J., Yizhar, O., & Schmitz, D. (2022). Optogenetics at the presynapse. Nature Neuroscience 2022 25:8, 25(8), 984-998. https://doi.org/10.1038/s41593-022-01113-6
Sandeep Ganesh, G., Konduri, P., Kolusu, A. S., Namburi, S. V., Chunduru, B. T. C., Nemmani, K. V. S., & Samudrala, P. K. (2023). Neuroprotective Effect of Saroglitazar on Scopolamine-Induced Alzheimer’s in Rats: Insights into the Underlying Mechanisms. ACS Chemical Neuroscience, 14(18), 3444-3459. https://doi.org/10.1021/acschemneuro.3c00320
Seifhosseini, S., Jahanshahi, M., Moghimi, A., & Aazami, N.-S. (2011). The Effect of Scopolamine on Avoidance Memory and Hippocampal Neurons in Male Wistar Rats. Basic and Clinical Neuroscience, 3(1), 9-15. https://bcn.iums.ac.ir/article-1-190-fa.html
Sorrells, S. F., Paredes, M. F., Zhang, Z., Kang, G., Pastor-Alonso, O., Biagiotti, S., Page, C. E., Sandoval, K., Knox, A., Connolly, A., Huang, E. J., Garcia-Verdugo, J. M., Oldham, M. C., Yang, Z., & Alvarez-Buylla, A. (2021). Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus. The Journal of Neuroscience, 41(12), 2554-2565. https://doi.org/10.1523/JNEUROSCI.0676-20.2020
Van Praag, H., Shubert, T., Zhao, C., & Gage, F. H. (2005). Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice. The Journal of Neuroscience, 25(38), 8680-8685. https://doi.org/10.1523/JNEUROSCI.1731-05.2005
Vandam, D., Lenders, G., & Dedeyn, P. (2006). Effect of Morris water maze diameter on visual-spatial learning in different mouse strains. Neurobiology of Learning and Memory, 85(2), 164-172. https://doi.org/10.1016/j.nlm.2005.09.006
Yen, C., Lin, C. L., & Chiang, M. C. (2023). Exploring the Frontiers of Neuroimaging: A Review of Recent Advances in Understanding Brain Functioning and Disorders. Life, 13(7), 1472. https://doi.org/10.3390/LIFE13071472
Yermakov, L. M., Griggs, R. B., Drouet, D. E., Sugimoto, C., Williams, M. T., Vorhees, C. V., & Susuki, K. (2019). Impairment of cognitive flexibility in type 2 diabetic db/db mice. Behavioural Brain Research, 371, 111978. https://doi.org/10.1016/J.BBR.2019.111978
Yeung, S. T., Martinez-Coria, H., Ager, R. R., Rodriguez-Ortiz, C. J., Baglietto-Vargas, D., & LaFerla, F. M. (2015). Repeated cognitive stimulation alleviates memory impairments in an Alzheimer’s disease mouse model. Brain Research Bulletin, 117, 10-15. https://doi.org/10.1016/j.brainresbull.2015.07.001
Zhang, S., Yang, W., Mou, H., Pei, Z., Li, F., & Wu, X. (2024). An Overview of Brain Fingerprint Identification Based on Various Neuroimaging Technologies. IEEE Transactions on Cognitive and Developmental Systems, 16(1), 151-164. https://doi.org/10.1109/TCDS.2023.3314155
Zhao, H., Jiang, Y. H., & Zhang, Y. Q. (2018). Modeling Autism in Non-Human Primates: Opportunities and Challenges. Autism Research: Official Journal of the International Society for Autism Research, 11(5), 686-694. https://doi.org/10.1002/AUR.1945
Zheng, Y. B., Shi, L., Zhu, X. M., Bao, Y. P., Bai, L. J., Li, J. Q., Liu, J. J., Han, Y., Shi, J., & Lu, L. (2021). Anticholinergic drugs and the risk of dementia: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 127, 296-306. https://doi.org/10.1016/J.NEUBIOREV.2021.04.031
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