Behavioral Paradigms in Rodent Models of Amyotrophic Lateral Sclerosis
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Abstract
Amyotrophic lateral sclerosis (ALS) remains an untreatable neurodegenerative disease without a cure or effective treatment, mainly due to elusive underlying mechanisms. ALS is primarily characterized by motor neuron dysfunction in the brain and spinal cord. However, it also exhibits non-motor symptoms such as executive, behavioral, and language dysfunction, making it challenging to establish informative disease models for relevant preclinic and clinical research. The discovery of ALS-causing genes has paved the way for the development of various animal models. Among these models, rodents have emerged as particularly valuable, demonstrating unique ALS-related behavioral defects in multiple behavioral tests. These models enable further understanding of disease mechanisms and provide sensitive and precise functional assessments for drug development. Given the intricate nature of ALS pathology, it is crucial and challenging to select appropriate behavioral tests as functional exploratory readouts, mainly due to the diverse array of ALS rodent models exhibiting distinct behavioral paradigms. Therefore, this report endeavors to present an overview of various behavioral assessments, encompassing motion ability tests, cognitive evaluations, sensory analyses, and other paradigms described in rodent models of ALS. Our goal is to summarize and compare the behavioral alterations observed in diverse rodent models of ALS with distinct gene mutations, thus providing comprehensive references and guidance for advancing pathogenic and therapeutic research in ALS.
Keywords:
Behavioral paradigms, Amyotrophic lateral sclerosis, SOD1, Motor defect
Article Details
How to Cite
ZHENG, Yaochao; HANKIN, Rachel; YAO, Yao.
Behavioral Paradigms in Rodent Models of Amyotrophic Lateral Sclerosis.
Medical Research Archives, [S.l.], v. 12, n. 1, feb. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4995>. Date accessed: 16 may 2024.
doi: https://doi.org/10.18103/mra.v12i1.4995.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Gurney ME, Pu H, Chiu AY, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. Jun 17 1994;264(5166):1772-5. doi:10.1126/science.8209258
3. Kafkafi N, Yekutieli D, Yarowsky P, Elmer GI. Data mining in a behavioral test detects early symptoms in a model of amyotrophic lateral sclerosis. Behav Neurosci. Aug 2008;122(4):777-87. doi:10.1037/0735-7044.122.4.777
4. Hayworth CR, Gonzalez-Lima F. Pre-symptomatic detection of chronic motor deficits and genotype prediction in congenic B6.SOD1(G93A) ALS mouse model. Neuroscience. Dec 15 2009;164(3):975-85. doi:10.1016/j.neuroscience.2009.08.031
5. Quarta E, Bravi R, Scambi I, Mariotti R, Minciacchi D. Increased anxiety-like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model. J Comp Neurol. Aug 1 2015;523(11):1622-38. doi:10.1002/cne.23759
6. Mukhamedyarov MA, Rizvanov AA, Safiullov ZZ, et al. Analysis of the efficiency of gene-cell therapy in transgenic mice with amyotrophic lateral sclerosis phenotype. Bull Exp Biol Med. Feb 2013;154(4):558-61. doi:10.1007/s10517-013-1999-2
7. Wooley CM, Sher RB, Kale A, Frankel WN, Cox GA, Seburn KL. Gait analysis detects early changes in transgenic SOD1(G93A) mice. Muscle Nerve. Jul 2005;32(1):43-50. doi:10.1002/mus.20228
8. Hadzipasic M, Ni W, Nagy M, et al. Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice. Proc Natl Acad Sci U S A. Nov 22 2016;113(47):E7600-e7609. doi:10.1073/pnas.1616832113
9. Guillot TS, Asress SA, Richardson JR, Glass JD, Miller GW. Treadmill gait analysis does not detect motor deficits in animal models of Parkinson's disease or amyotrophic lateral sclerosis. J Mot Behav. Nov 2008;40(6):568-77. doi:10.3200/jmbr.40.6.568-577
10. Hampton TG, Amende I. Treadmill gait analysis characterizes gait alterations in Parkinson's disease and amyotrophic lateral sclerosis mouse models. J Mot Behav. Jan-Feb 2010;42(1):1-4. doi:10.1080/00222890903272025
11. Mancuso R, Oliván S, Osta R, Navarro X. Evolution of gait abnormalities in SOD1(G93A) transgenic mice. Brain Res. Aug 11 2011;1406:65-73. doi:10.1016/j.brainres.2011.06.033
12. Vergouts M, Marinangeli C, Ingelbrecht C, et al. Early ALS-type gait abnormalities in AMP-dependent protein kinase-deficient mice suggest a role for this metabolic sensor in early stages of the disease. Metab Brain Dis. Dec 2015;30(6):1369-77. doi:10.1007/s11011-015-9706-9
13. Schäfer S, Hermans E. Reassessment of motor-behavioural test analyses enables the detection of early disease-onset in a transgenic mouse model of amyotrophic lateral sclerosis. Behav Brain Res. Nov 20 2011;225(1):7-14. doi:10.1016/j.bbr.2011.06.019
14. Lepore AC, Tolmie C, O'Donnell J, et al. Peripheral hyperstimulation alters site of disease onset and course in SOD1 rats. Neurobiol Dis. Sep 2010;39(3):252-64. doi:10.1016/j.nbd.2010.03.021
15. Morrison BM, Lachey Jl Fau - Warsing LC, Warsing Lc Fau - Ting BL, et al. A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis. (1090-2430 (Electronic))
16. Weydt P, Hong Sy Fau - Kliot M, Kliot M Fau - Möller T, Möller T. Assessing disease onset and progression in the SOD1 mouse model of ALS. (0959-4965 (Print))
17. Flis DJ, Dzik K, Kaczor JJ, et al. Swim Training Modulates Mouse Skeletal Muscle Energy Metabolism and Ameliorates Reduction in Grip Strength in a Mouse Model of Amyotrophic Lateral Sclerosis. Int J Mol Sci. Jan 9 2019;20(2)doi:10.3390/ijms20020233
18. Zhao J, Cooper LT, Boyd AW, Bartlett PF. Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1(G93A) ALS mouse model. Sci Rep. Jul 30 2018;8(1):11393. doi:10.1038/s41598-018-29845-1
19. Liu L, Killoy KM, Vargas MR, Yamamoto Y, Pehar M. Effects of RAGE inhibition on the progression of the disease in hSOD1(G93A) ALS mice. Pharmacol Res Perspect. Aug 2020;8(4):e00636. doi:10.1002/prp2.636
20. Koza LA, Winter AN, Holsopple J, et al. Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis. Nutrients. Jun 18 2020;12(6) doi:10.3390/nu12061824
21. Gross SK, Shim BS, Bartus RT, et al. Focal and dose-dependent neuroprotection in ALS mice following AAV2-neurturin delivery. Exp Neurol. Jan 2020;323:113091. doi:10.1016/j.expneurol.2019.113091
22. Cai M, Yang EJ. Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model. Nutrients. Nov 4 2019;11(11)doi:10.3390/nu11112644
23. Kim J, Kim TY, Cho KS, Kim HN, Koh JY. Autophagy activation and neuroprotection by progesterone in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. Nov 2013;59:80-5. doi:10.1016/j.nbd.2013.07.011
24. Yoo YE, Ko CP. Treatment with trichostatin A initiated after disease onset delays disease progression and increases survival in a mouse model of amyotrophic lateral sclerosis. Exp Neurol. Sep 2011;231(1):147-59. doi:10.1016/j.expneurol.2011.06.003
25. Yoo YE, Ko CP. Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice. PLoS One. 2012;7(5):e37258. doi:10.1371/journal.pone.0037258
26. Naor S, Keren Z, Bronshtein T, Goren E, Machluf M, Melamed D. Development of ALS-like disease in SOD-1 mice deficient of B lymphocytes. J Neurol. Aug 2009;256(8):1228-35. doi:10.1007/s00415-009-5097-3
27. Gill A, Kidd J, Vieira F, Thompson K, Perrin S. No benefit from chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using a standard mouse model of familial ALS. PLoS One. Aug 3 2009;4(8):e6489. doi:10.1371/journal.pone.0006489
28. Zeldich E, Chen CD, Boden E, et al. Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1(G93A)) Mouse Model of ALS. J Mol Neurosci. Oct 2019;69(2):264-285. doi:10.1007/s12031-019-01356-2
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