Temporal and Spatial Dynamics of Motor Dysfunction in Preclinical Parkinson’s Disease and Aging-Journal of Psychiatry and Brain Science-CSCIED科技核心评价数据库-手机版

Temporal and Spatial Dynamics of Motor Dysfunction in Preclinical Parkinson’s Disease and Aging

Temporal and Spatial Dynamics of Motor Dysfunction in Preclinical Parkinson’s Disease and Aging

ES评分 0 浏览量：126 下载量：0

DOI	10.20900/jpbs.20250009
刊名	Journal of Psychiatry and Brain Science JPBS
年，卷(期)	2025, 10(4)
作者	Navya Nair,Grace Hey,Alexander Becsey,Tara Kari,Xavier Becsey,Julia Root,Vinata Vedam-Mai*,
作者单位	Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, FL 32611, USA ; Norman Fixel Institute for Neurological Diseases, College of Medicine, University of Florida, Gainesville, FL 32608, USA ; Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, FL 32611, USA ;
摘要	Gait assessments have been performed in several murine models of Parkinson’s Disease (PD), but the M83+/− mouse model of PD has been relatively understudied in this context. Metrics of gait swing, stride length and frequency, and ataxia were collected in M83+/− mice with peripheral injections of α-syn preformed fibrils (PFF) and in aged M83+/− mice without fibrils using the DigiGait™ system. PFF-mice showed significantly decreased swing in all limbs (0.11 ± 0.02 vs. 0.13 ± 0.03, p = 0.007) compared to age-matched controls. Stride frequency was significantly increased in all limbs (3.9 ± 0.4 vs. 3.0 ± 0.5, p = 0.010) of PFF-treated mice. Swing was significantly greater in the hindlimbs of young M83+/−+PFF mice compared to aged M83+/− mice (0.11 (0.5) vs. 0.08 (0.3), p = 0.015). Ataxia was significantly higher in young M83+/−+PFF mice compared to control for forelimbs (1.1 ± 1.0 vs. 0.6 ± 0.5, p = 0.027), hindlimbs (0.9 ± 1.0 vs. 0.3 ± 0.2, p = 0.016), and all limbs (1.0 ± 1.0 vs. 0.3 ± 0.5, p = 0.015). M83+/− mice demonstrate significant gait abnormalities consistent with features of PD. This study supports the utility of the M83+/− murine model for preclinical gait analyses in PD.
Abstract	Gait assessments have been performed in several murine models of Parkinson’s Disease (PD), but the M83+/− mouse model of PD has been relatively understudied in this context. Metrics of gait swing, stride length and frequency, and ataxia were collected in M83+/− mice with peripheral injections of α-syn preformed fibrils (PFF) and in aged M83+/− mice without fibrils using the DigiGait™ system. PFF-mice showed significantly decreased swing in all limbs (0.11 ± 0.02 vs. 0.13 ± 0.03, p = 0.007) compared to age-matched controls. Stride frequency was significantly increased in all limbs (3.9 ± 0.4 vs. 3.0 ± 0.5, p = 0.010) of PFF-treated mice. Swing was significantly greater in the hindlimbs of young M83+/−+PFF mice compared to aged M83+/− mice (0.11 (0.5) vs. 0.08 (0.3), p = 0.015). Ataxia was significantly higher in young M83+/−+PFF mice compared to control for forelimbs (1.1 ± 1.0 vs. 0.6 ± 0.5, p = 0.027), hindlimbs (0.9 ± 1.0 vs. 0.3 ± 0.2, p = 0.016), and all limbs (1.0 ± 1.0 vs. 0.3 ± 0.5, p = 0.015). M83+/− mice demonstrate significant gait abnormalities consistent with features of PD. This study supports the utility of the M83+/− murine model for preclinical gait analyses in PD.
关键词	Parkinson’s disease; murine model; gait; M83+/−
KeyWord	Parkinson’s disease; murine model; gait; M83+/−
基金项目
页码	-

参考文献
相关文献

1.Broom L, Ellison BA, Worley A, Wagenaar L, Sorberg E, Ashton C, et al. A translational approach to capture gait signatures of neurological disorders in mice and humans. Sci Rep. 2017;7(1):3225.
2.Spillantini MG, Schmidt ML, Lee VMY, Trojanowski JQ, Jakes R, Goedert M. α-Synuclein in Lewy bodies. Nature. 1997;388(6645):839-40.
3.Hausdorff JM, Cudkowicz ME, Firtion R, Wei JY, Goldberger AL. Gait variability and basal ganglia disorders: Stride-to-stride variations of gait cycle timing in parkinson's disease and Huntington's disease. Mov Disord. 2004;13(3):428-37.
4.Blin O, Ferrandez AM, Serratrice G. Quantitative analysis of gait in Parkinson patients: Increased variability of stride length. J Neurol Sci. 1990;98(1):91-7.
5.Frenkel-Toledo S, Giladi N, Peretz C, Herman T, Gruendlinger L, Hausdorff JM. Effect of gait speed on gait rhythmicity in Parkinson's disease: Variability of stride time and swing time respond differently. J Neuroeng Rehabil. 2005;2(1):23.
6.Yogev G, Giladi N, Peretz C, Springer S, Simon ES, Hausdorff JM. Dual tasking, gait rhythmicity, and Parkinson's disease: Which aspects of gait are attention demanding? Eur J Neurosci. 2005;22(5):1248-56.
7.Snijders AH, Leunissen I, Bakker M, Overeem S, Helmich RC, Bloem BR, et al. Gait-related cerebral alterations in patients with Parkinson’s disease with freezing of gait. Brain. 2011;134(1):59-72.
8.Bohnen NI, Jahn K. Imaging: What can it tell us about parkinsonian gait? Mov Disord. 2013;28(11):1492-500.
9.Maurits NM, Ferraye MU, Debû B, Heil L, Carpenter M, Bloem BR, et al. Using Motor Imagery to Study the Neural Substrates of Dynamic Balance. PLoS ONE. 2014;9(3):e91183.
10.Zach H, Janssen AM, Snijders AH, Delval A, Ferraye MU, Auff E, et al. Identifying freezing of gait in Parkinson's disease during freezing provoking tasks using waist-mounted accelerometry. Parkinsonism Relat Disord. 2015;21(11):1362-6.
11.Giladi N, Horak FB, Hausdorff JM. Classification of gait disturbances: Distinguishing between continuous and episodic changes. Mov Disord. 2013;28(11):1469-73.
12.Bilney B, Morris ME, Churchyard A, Chiu E, Georgiou-Karistianis N. Evidence for a disorder of locomotor timing in Huntington's disease. Mov Disord. 2004;20(1):51-7.
13.Sargent D, Verchere J, Lazizzera C, Gaillard D, Lakhdar L, Streichenberger N, et al. 'Prion-like' propagation of the synucleinopathy of M83 transgenic mice depends on the mouse genotype and type of inoculum. J Neurochem. 2017;143(1):126-35.
14.Klein C, Westenberger A. Genetics of Parkinson's Disease. Cold Spring Harb Perspect Med. 2012;2(1):a008888-a.
15.Cregg JM, Sidhu SK, Leiras R, Kiehn O. Basal ganglia–spinal cord pathway that commands locomotor gait asymmetries in mice. Nat Neurosci. 2024;27(4):716-27.
16.Chidambaram SB, Song B-J, Priyadarshini P, Mahalakshmi AM, Shivalinga A, Nagaraju PG, et al. Telmisartan Protects Mitochondrial Function, Gait, and Neuronal Apoptosis by Activating the Akt/GSK3β/PGC1α Pathway in an MPTP-Induced Mouse Model of Parkinson's Disease. J Integr Neurosci. 2024;23(2):29.
17.Nie L, He K, Qiu C, Li Q, Xiong B, Gao C, et al. Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway. Biomed Pharmacother. 2024;173:116415.
18.Hack W, Gladen-Kolarsky N, Chatterjee S, Liang Q, Maitra U, Ciesla L, et al. Gardenin A treatment attenuates inflammatory markers, synuclein pathology and deficits in tyrosine hydroxylase expression and improves cognitive and motor function in A53T-α-syn mice. Biomed Pharmacother. 2024;173:116370.
19.Sacino AN, Brooks M, Thomas MA, McKinney AB, Lee S, Regenhardt RW, et al. Intramuscular injection of alpha-synuclein induces CNS alpha-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci USA. 2014;111(29):10732-7.
20.Cookson MR, Paumier KL, Sukoff Rizzo SJ, Berger Z, Chen Y, Gonzales C, et al. Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease. PLoS ONE. 2013;8(8):e70274.
21.Elble RJ, Cousins R, Leffler K, Hughes L. Gait initiation by patients with lower-half parkinsonism. Brain. 1996;119(Pt 5):1705-16.
22.Morris ME, Iansek R, Matyas TA, Summers JJ. Stride length regulation in Parkinson's disease. Normalization strategies and underlying mechanisms. Brain. 1996;119(Pt 2):551-68.
23.Wu T, Hallett M, Chan P. Motor automaticity in Parkinson's disease. Neurobiol Dis. 2015;82:226-34.
24.Zampier VC, Vitorio R, Beretta VS, Jaimes DAR, Orcioli-Silva D, Santos PCR, et al. Gait bradykinesia and hypometria decrease as arm swing frequency and amplitude increase. Neurosci Lett. 2018;687:248-52.
25.Kwon KY, Kim M, Lee SM, Kang SH, Lee HM, Koh SB. Is reduced arm and leg swing in Parkinson's disease associated with rigidity or bradykinesia? J Neurol Sci. 2014;341(1-2):32-5.
26.Camargo CHF, Ferreira-Peruzzo SA, Ribas DIR, Franklin GL, Teive HAG. Imbalance and gait impairment in Parkinson's disease: Discussing postural instability and ataxia. Neurol Sci. 2024;45(4):1377-88.
27.Kim SD, Allen NE, Canning CG, Fung VS. Postural instability in patients with Parkinson's disease. Epidemiology, pathophysiology and management. CNS Drugs. 2013;27(2):97-112.
28.Jankovic J. Parkinson's disease: Clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368-76.
29.Lewek MD, Poole R, Johnson J, Halawa O, Huang X. Arm swing magnitude and asymmetry during gait in the early stages of Parkinson's disease. Gait Posture. 2010;31(2):256-60.
30.Miller-Patterson C, Buesa R, McLaughlin N, Jones R, Akbar U, Friedman JH. Motor asymmetry over time in Parkinson's disease. J Neurol Sci. 2018;393:14-7.
31.Holmes AA, Matarazzo M, Mondesire-Crump I, Katz E, Mahajan R, Arroyo-Gallego T. Exploring Asymmetric Fine Motor Impairment Trends in Early Parkinson's Disease via Keystroke Typing. Mov Disord Clin Pract. 2023;10(10):1530-5.
32.Nieuwboer A, Dom R, De Weerdt W, Desloovere K, Fieuws S, Broens-Kaucsik E. Abnormalities of the spatiotemporal characteristics of gait at the onset of freezing in Parkinson's disease. Mov Disord. 2001;16(6):1066-75.
33.Tullo S, Miranda AS, Del Cid-Pellitero E, Lim MP, Gallino D, Attaran A, et al. Neuroanatomical and cognitive biomarkers of alpha-synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms. J Neurochem. 2024;168(8):1546-64.

引用本文

Navya Nair,Grace Hey,Alexander Becsey,Tara Kari,Xavier Becsey,Julia Root,Vinata Vedam-Mai*. Temporal and Spatial Dynamics of Motor Dysfunction in Preclinical Parkinson’s Disease and Aging [J]. Journal of Psychiatry and Brain Science. 2025; 10; (4). - .

文献评论

相关学者

相关机构