The Morris Water Maze is a simple yet highly effective method for evaluating cognitive function, central to neurodegenerative disease research. Defects in spatial learning and memory caused by neurodegenerative diseases can be accurately assessed using the Morris Water Maze model, providing all-important insights into the processes underlying the progression of neurodegenerative diseases and the evaluation of the effectiveness of treatments.
Neurodegenerative diseases, the progressive loss of brain and/or spinal cord neurons, are a major challenge to health systems across the globe. In some cases, neurodegenerative disorders are the second-most prevalent cause of death after cardiovascular diseases.1 Incidences of neurodegenerative diseases and resulting deaths are increasing with the current rapidly aging population. The most common neurodegenerative disorders are dementias, which affect around seven million people, and this estimation is predicted to double by 2040.2
The major problem with neurodegenerative disorders is that there is currently no cure or proper treatment because the mechanisms that cause them are not completely understood.3 There is, therefore, an urgent need to develop new, more effective, and safer treatments in neurodegenerative disease research, along with enhanced methods for earlier diagnosis.2
To this end, a tool that has proven indispensable in neurodegenerative disease research is the Morris Water Maze protocol. First described by Michael Morris in the 1980s, the Morris Water Maze is a universal protocol for testing normal cognitive function and can effectively detect any deviations in memory function.4
What is the Morris Water Maze experiment?
The Morris Water Maze experiment is a simple, spatial task for examining learning and memory in rodents. In the Morris Water Maze experiment, the rodent must swim in a tank to find a hidden platform using spatial cues memorized during pre-training.5 The assessment of the rodent’s spatial memory occurs within the framework of the Morris Water Maze protocol, where both the time it takes for the rodent to locate the platform and the efficiency of their direct route to the platform is observed.
The Morris Water Maze experiment can be used to compare the cognitive function of wild-type or neurodegenerative-prone rodents to identify the molecular mechanisms potentially underpinning these diseases; this method is regularly used in the study of Alzheimer’s disease (AD), for example.5 There are a range of different Morris Water Maze protocols which involve different mechanisms of navigation and can detect defects in the cognitive function of brain areas essential in learning and memory other than just the hippocampus.6
Understanding the progression and treatment of neurodegenerative diseases using the Morris Water Maze
Knowledge of the progression of neurodegenerative diseases is necessary for developing more effective treatments for these diseases. Morris Water Maze experiments have been used to evaluate the role of enzymes expressed in the brain that are involved in the progression of neuroinflammatory in AD. The role of the sEH enzyme in the development of AD was recently highlighted using the Morris Water Maze experiment, and research suggests that sEH is a vital regulator in the progression of AD and could be a potential therapeutic target for delaying the progression of AD.7
The Morris Water Maze experiments have been utilized to investigate the impact of overactive microglia on cognitive decline in Parkinson’s disease (PD). By assessing the cognitive performance of mice through this experiment, researchers explored the role of microglia in rotenone-induced cognitive deficits. The findings suggest that activated microglia contribute to cognitive impairments through processes like neuroinflammation, apoptosis, and oxidative stress. These new insights have significantly enhanced our understanding of the immunopathogenesis underlying cognitive defects in PD.
The significance of Morris Water Maze experiments also extends to exploring potential synergistic treatment approaches for enhanced effectiveness. A recent study exemplified this using the Morris Water Maze model to demonstrate the positive interactions between memantine and cholinesterase inhibitors. The combination of these treatments was found to be more effective than individual monotreatments, 9 providing valuable insights into potential complementary therapies.
Conclusion
Thanks to its simplicity and effectiveness, the Morris Water Maze has great utility in neurodegenerative research and is particularly important in understanding the progression of these diseases and the identification of potential treatments. With the increasing trend in cases of neurodegenerative diseases, the Morris Water Maze could not be more fundamental to gaining insights to help combat the devastating effects of neurodegenerative diseases on worldwide health.
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References
- Gitler, A.D., Dhillon, P. and Shorter, J. 2017. Neurodegenerative disease: models, mechanisms, and a new hope. Disease models & mechanisms. 10(5), pp.499-502.
- Zahra, W., Rai, S.N., Birla, H., Singh, S.S., Dilnashin, H., Rathore, A.S. and Singh, S.P. 2020. The global economic impact of neurodegenerative diseases: Opportunities and challenges. Bioeconomy for sustainable development. Pp.333-345.
- Durães, F., Pinto, M. and Sousa, E. 2018. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals. 11(2), p.44.
- Morris, R. 1984. Developments of a water-maze procedure for studying spatial learning in the rat. Journal of neuroscience methods. 11(1), pp.47-60.
- Zhang, W. and Luo, P. 2020. Myocardial infarction predisposes neurodegenerative diseases. Journal of Alzheimer’s Disease. 74(2), pp.579-587.
- Mulder, G.B. and Pritchett, K. 2003. The Morris water maze. Journal of the American Association for Laboratory Animal Science. 42(2), pp.49-50.
- Lee, H.T., Lee, K.I., Chen, C.H. and Lee, T.S. 2019. Genetic deletion of soluble epoxide hydrolase delays the progression of Alzheimer’s disease. Journal of Neuroinflammation. 16, pp.1-12.
- Zhang, D., Li, S., Hou, L., Jing, L., Ruan, Z., Peng, B., Zhang, X., Hong, J.S., Zhao, J. and Wang, Q. 2021. Microglial activation contributes to cognitive impairments in rotenone-induced mouse Parkinson’s disease model. Journal of neuroinflammation. 18, pp.1-16.
- Bruszt, N., Bali, Z.K., Tadepalli, S.A., Nagy, L.V. and Hernádi, I. 2021. Potentiation of cognitive enhancer effects of Alzheimer’s disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task. Psychopharmacology. 238(11), pp.3273-3281.