Investigating the temporal characteristics of motor learning deficits in Thy 1-SNCA early Parkinson's disease model mice

doi:10.3969/j.issn.1006-7795.2024.05.021

Abstract

Abstract: Objective In this experiment, a mouse model of early Parkinson's (PD) disease was established to explore the temporal characteristics of PD motor learning deficits. Methods Six-month-old Thy 1-SNCA transgenic mice were selected as an early PD model and compared with wild type (WT) mice for analysis. The mice's motor function and spatial working memory ability were assessed by experiments such as open field test, pole test, and Y-maze test, and the typical accelerating rotarod test was used as a behavioral paradigm for motor learning. Results The six-month-old Thy 1-SNCA transgenic mice did not show abnormalities in motor function and spatial working memory ability, but presented obvious characteristics of motor learning deficits. Conclusions Specific motor learning deficits exist on early PD model mice, which can be used as a detection indicator of early PD. And the typical accelerating rotarod test can be used as a key behavioral method for detecting motor learning deficits in PD.

Key words: Parkinson's disease, early Parkinson's disease model, motor learning deficits, motor symptoms

CLC Number:

R741.02

Fu Wenxin, Wang Tie, Yang Runing, Qu Mingqin, Gao Ge, Yang Hui, Ja Jun. Investigating the temporal characteristics of motor learning deficits in Thy 1-SNCA early Parkinson's disease model mice[J]. Journal of Capital Medical University, 2024, 45(5): 881-890.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2024.05.021

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2024/V45/I5/881

References

［1］闫睿, 魏婧, 贾军, 等. 皮层-基底神经节环路beta振荡与帕金森病运动障碍的关系［Ｊ］. 生理科学进展, 2022, 53(4): 254－258.
［2］Smiley-Oyen A L, Worringham C J, Cross C L. Motor learning processes in a movement-scaling task in olivopontocerebellar atrophy and Parkinson's disease［Ｊ］. Exp Brain Res, 2003, 152(4)：453－465.
［3］Olson M, Lockhart T E, Lieberman A. Motor learning deficits in Parkinson's disease (PD) and their effect on training response in gait and balance: a narrative review［Ｊ］. Front Neurol, 2019, 10: 62.
［4］Wu T, Hallett M, Chan P. Motor automaticity in Parkinson's disease［Ｊ］. Neurobiol Dis, 2015, 82: 226－234.
［5］Tzvi E, Bey R, Nitschke M, et al. Motor sequence learning deficits in idiopathic Parkinson's disease are associated with increased substantia nigra activity［Ｊ］. Front Aging Neurosci, 2021, 13: 685168.
［6］He Y, Huang L, Wang K, et al. α-synuclein selectively impairs motor sequence learning and value sensitivity: reversal by the adenosine A2A receptor antagonists［Ｊ］. Cereb Cortex, 2022, 32(4): 808－823.
［7］González-Rodríguez P, Zampese E, Stout K A, et al. Disruption of mitochondrial complex I induces progressive parkinsonism［Ｊ］. Nature, 2021, 599(7886): 650－656.
［8］Kupferschmidt D A, Juczewski K, Cui G H, et al. Parallel, but dissociable， processing in discrete corticostriatal inputs encodes skill learning［Ｊ］. Neuron, 2017, 96(2): 476－489.
［9］Reinius B, Blunder M, Brett F M, et al. Conditional targeting of medium spiny neurons in the striatal matrix［Ｊ］. Front Behav Neurosci, 2015, 9: 71.
［10］Kraeuter A K, Guest P C, Sarnyai Z. The open field test for measuring locomotor activity and anxiety-like behavior［Ｊ］. Methods Mol Biol, 2019, 1916: 99－103.
［11］Bouet V, Boulouard M, Toutain J, et al. The adhesive removal test: a sensitive method to assess sensorimotor deficits in mice［Ｊ］. Nat Protoc, 2009, 4(10): 1560－1564.
［12］Kraeuter A K, Guest P C, Sarnyai Z. The Y-maze for assessment of spatial working and reference memory in mice［Ｊ］. Methods Mol Biol, 2019, 1916: 105－111.
［13］Ogawa N, Hirose Y, Ohara S, et al. A simple quantitative bradykinesia test in MPTP-treated mice［Ｊ］. Res Commun Chem Pathol Pharmacol, 1985, 50(3): 435－441.
［14］Buitrago M M, Schulz J B, Dichgans J, et al. Short and long-term motor skill learning in an accelerated rotarod training paradigm［Ｊ］. Neurobiol Learn Mem, 2004, 81(3): 211－216.
［15］Rockenstein E, Mallory M, Hashimoto M, et al. Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters［Ｊ］. J Neurosci Res, 2002, 68(5): 568－578.
［16］Li R L, Lu Y Q, Zhang Q D, et al. Piperine promotes autophagy flux by P2RX4 activation in SNCA/α-synuclein-induced Parkinson disease model［Ｊ］. Autophagy, 2022, 18(3): 559－575.
［17］Chesselet M F, Richter F, Zhu C N, et al. A progressive mouse model of Parkinson's disease: the Thy 1-aSyn (“Line 61”) mice［Ｊ］. Neurotherapeutics, 2012, 9(2): 297－314.
［18］Shiotsuki H, Yoshimi K, Shimo Y, et al. A rotarod test for evaluation of motor skill learning［Ｊ］. J Neurosci Methods, 2010, 189(2): 180－185.
［19］Lam HA, Wu N, Cely I, et al. Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human α-synuclein［Ｊ］. J Neurosci Res, 2011, 89(7): 1091－1102.
［20］Chiu C C, Weng Y H, Yeh T H, et al. Deficiency of RAB39B activates ER stress-induced pro-apoptotic pathway and causes mitochondrial dysfunction and oxidative stress in dopaminergic neurons by impairing autophagy and upregulating α-Synuclein［Ｊ］. Mol Neurobiol, 2023, 60(5): 2706－2728.
［21］Colla E, Jensen P H, Pletnikova O, et al. Accumulation of toxic α-synuclein oligomer within endoplasmic reticulum occurs in α-synucleinopathy in vivo［Ｊ］. J Neurosci, 2012, 32(10): 3301－3305.
［22］Choi B K, Choi M G, Kim J Y, et al. Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking［Ｊ］. Proc Natl Acad Sci USA, 2013, 110(10): 4087－4092.
［23］Chesselet M F, Richter F. Modelling of Parkinson's disease in mice［Ｊ］. Lancet Neurol, 2011, 10(12): 1108－1118.
［24］Gerfen C R, Keefe K A, Gauda E B. D1 and D2 dopamine receptor function in the striatum: coactivation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons［Ｊ］. J Neurosci, 1995, 15(12): 8167－8176.
［25］Bartels A L, Leenders K L. Parkinson's disease: the syndrome, the pathogenesis and pathophysiology［Ｊ］. Cortex, 2009, 45(8): 915－921.
［26］Dan X J, King B R, Doyon J, et al. Motor sequence learning and consolidation in unilateral de novo patients with Parkinson's disease［Ｊ］. PLoS One, 2015, 10(7): e0134291.
［27］Fleming S M, Tetreault N A, Mulligan C K, et al. Olfactory deficits in mice overexpressing human wildtype alpha-synuclein［Ｊ］. Eur J Neurosci, 2008, 28(2): 247－256.
［28］Braak H, Tredici K D, Rüb U, et al. Staging of brain pathology related to sporadic Parkinson's disease［Ｊ］. Neurobiol Aging, 2003, 24(2): 197－211.
［29］Taylor T N, Caudle W M, Shepherd K R, et al. Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity［Ｊ］. J Neurosci, 2009, 29(25): 8103－8113.
［30］Langston J W. The Parkinson's complex: parkinsonism is just the tip of the iceberg［Ｊ］. Ann Neurol, 2006, 59(4): 591－596.
［31］Xu T H, Wang S F, Lalchandani R R, et al. Motor learning in animal models of Parkinson's disease: aberrant synaptic plasticity in the motor cortex［Ｊ］. Mov Disord, 2017, 32(4): 487－497.
［32］Wu N P, Joshi P R, Cepeda C, et al. Alpha-synuclein overexpression in mice alters synaptic communication in the corticostriatal pathway［Ｊ］. J Neurosci Res, 2010, 88(8): 1764－1776.
［33］Morris R G. D.O. Hebb: the organization of behavior, Wiley: New York; 1949［Ｊ］. Brain Res Bull, 1999, 50(5－6): 437.
［34］Roberts B M, Doig N M, Brimblecombe K R, et al. GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model［Ｊ］. Nat Commun, 2020, 11(1): 4958.
［35］Xu T H, Yu X Z, Perlik A J, et al. Rapid formation and selective stabilization of synapses for enduring motor memories［Ｊ］. Nature, 2009, 462(7275): 915－919.
［36］Guo L L, Xiong H, Kim J I, et al. Dynamic rewiring of neural circuits in the motor cortex in mouse models of Parkinson's disease［Ｊ］. Nat Neuro sci, 2015, 18: 1299－1309.
［37］Cao V Y, Ye Y Z, Mastwal S, et al. Motor learning consolidates arc-expressing neuronal ensembles in secondary motor cortex［Ｊ］. Neuron, 2015, 86(6): 1385－1392.
［38］Jakkamsetti V， Scudder W， Kathote G， et al. Quantification of early learning and movement sub-structure predictive of motor performanc［Ｊ］. Sci Rep, 2021, 11(1)：14405.

[1]	Yuan Huili, Gong Xiaoli, Fan Zheng, Liang Zhigang, Wang Xiaomin. Effects and mechanism of Tenuigenin on lipopolysaccharide induced Parkinson's disease model [J]. Journal of Capital Medical University, 2020, 41(6): 914-922.
[2]	Gong Xiaoli, Liu Mengru, Wang Le, Liu Yang, Zhang Ting, Sun Ying, Wang Xiaomin. Role of α-synuclein in microglia inflammation and phagocytosis [J]. Journal of Capital Medical University, 2018, 39(5): 693-698.
[3]	Liu Mengru, Gong Xiaoli, Wang Le, Liu Yang, Zhang Ting, Wang Xiaomin. Effect of lipopolysaccharide on the expression of α-synuclein in the intestinal tract [J]. Journal of Capital Medical University, 2018, 39(4): 557-562.
[4]	Liu Xuemei;Yu Shun;Li Yaohua;Zhou Ming;Zuo Xiaohong;Lü Guowei;Cheng Biao. Production and Characterization of an Antiserum Against Human α-synuclein [J]. Journal of Capital Medical University, 2003, 24(1): 7-10.
[5]	Zhang Jiajin;Zhai Jing;Chang Pengfei. Expression and Localization of BDNFmRNA to Neurons in the Brain Following Midbrain Reticular Formation Injury by in Situ Hybridization [J]. Journal of Capital Medical University, 2000, 21(1): 5-8.