Gait analysis in laboratory animals studying coordinated movement and associated disorders
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Transcript of Gait analysis in laboratory animals studying coordinated movement and associated disorders
Gait Analysis in Laboratory Animals: Studying Coordinated Movement and Associated Disorders
Sponsored by:
Martin HessInsideScientific
Tom Hampton, PhDMouse Specifics Inc.
Carol Milligan, PhDWake Forest School of
Medicine
Charles Meshul, PhDVA Medical Center/Portland & Oregon Health & Science
University
InsideScientific is an online educational environment designed for life science researchers. Our goal is to aid in
the sharing and distribution of scientific information regarding innovative technologies, protocols, research
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Thank you to our webinar sponsor
DigiGait is a widely published ventral plane videography instrumentation available for gait analysis in laboratory animals. Voluntary and treadmill walking, DigiGait performs gait analysis of mice and rats over a range of walking and running speeds. Learn More >>>
Gait analysis in animal models of human diseases –measures of strength, balance, & coordination
Thomas Hampton, PhD
President and CSO
Mouse Specifics, Inc.
Copyright 2015 T. Hampton, Mouse Specifics, Inc. & InsideScientific. All Rights Reserved.
What is gait analysis?
Gait analysis is the quantitative assessment of the manner of movement, as it applies to ambulation [walking and running].
When is gait disturbed?• Arthritis
• Bone fractures
• Traumatic Brain Injury• Amyotrophic lateral sclerosis• Ataxia
• Medulloblastoma• Spinal cord injury
• Huntington’s disease• Nerve injury• Orthopedic injuries
• Parkinson’s disease• Multiple sclerosis• Stroke• Muscular dystrophy
Amyotrophic lateral sclerosisDr. Carol Milligan
Parkinson’s diseaseDr. Charles Meshul
Why gait analysis?
Patients want to walk!
Why gait analysis?
Why treadmill gait analysis?
1. rodents rarely follow instructions
2. walking speed significantly impacts posture & kinematics
3. higher repeatability and lower standard error
4. explore challenge conditions to highlight subtle problems
5. early detection
What does gait analysis measure?
How long is my stride?
How far apart are my feet?
Do my toes point inwards?
Is my swing exaggerated?
How steady am I on my feet?
The DigiGait™ Imaging System, is patented instrumentation for studying gait by examining the ventral view of subjects as they walk on a transparent treadmill belt.
A high speed camera images the ventral view of animals as they walk, run, limp, or hop on the motorized transparent treadmill belt.
AI examines each paw to determine its position relative to the treadmill belt, resulting in gait signals for each limb.
Braking
PropulsionStance
Stride
Swing
Pa
w a
rea
Time
Multiple strides
Voluntary and treadmill
Range of speeds (0-100 cm/s)
Horizontal, incline, & decline
How do my animals walk?
Stride length
Stance width
Cadence
Paw placement angle
Swing time
Step-to-step stability
Braking duration
Propulsion duration
Gait symmetry
Paw overlap
Paw area
Tau
Rate of loading
Sciatic Functional Index
……….
18 cm/s
36 cm/s
Guinea PigEven small differences in walking speed significantly impact gait metrics, including stride length and paw angles.
Ensemble averaged gait signals:
note good symmetry between left & right forelimbs (top) & hind limbs (bottom).
Sciatic nerve
injury
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32 41 52 63 76 97 110
Life Day
Hin
d p
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pla
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t an
gle
(d
eg
rees)
Wild-type
SOD1 G93A
P<0.05
ALS model
PD model
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32 41 52 63 76 97 110
Life Day
Hin
d p
aw
pla
cem
en
t an
gle
(d
eg
rees)
Wild-type
SOD1 G93A
Stride length changes in
mouse ~0.5 cm.
“ we can’t just place a banana in front of a mouse to cause a disturbance”
Changing the properties of the walking surface primarily affected forelimb kinematics.
Oil applied to walking surface
Changing the properties of the walking surface primarily affected forelimb kinematics.
Oil applied to walking surface
How do lab animals manage obstacles in their walking path?
How are obstacles managed?
How might neurotoxins affect ability to detect and negotiate obstacles?
Baseline
Ethanol
Pnd 14 Pnd 25
Pnd 14
Study of developmental abnormalities
• Cerebral palsy
• Muscular dystrophy
• Spinal muscular atrophy
Huntington’s disease [3NP, R6/2]
Parkinson’s disease [MPTP, 6-hydroxydopamine]
Amyotrophic lateral sclerosis [TDP-43, SOD1 G93A]
MS
OA, RA, Pain
Stroke
Spinal Cord Injury
The DigiGait™ Imaging System is the most widely published treadmill gait analysis system available.
Recent Publications:
Sashindranath et al.....craniotomy and traumatic brain
injury. Behav Brain Res. 2015
Poulet et al. ...articular cartilage lesions.
Osteoarthritis Cartilage. 2015
Gadalla et al. Gait analysis in a Mecp2 knockout....
PLoS One. 2014
Benefits
In vivo
Easy-to-use
Turn-key solution
Scalable
Automated
Digital information
Relevant metrics of motion
Integrates strength, balance,
coordination
Replaces multiple motor
function tests
Visual record of study
Traumatic Brain Injury
ALS, HD, PD
Pain
Muscular dystrophy
Multiple sclerosis
Neuropathy
Drug screening
Features Benefits Applications
The DigiGait™ Imaging System has features that bring benefits to numerous disease applications.
Behavioral Deficits Correlate with Early Pathology in the SOD1 mouse model of ALS
Carol Milligan, Ph.D.
Professor, Department of
Neurobiology & AnatomyWake Forest School of Medicine
Copyright 2015 C. Milligan, Mouse Specifics Inc. & InsideScientific. All Rights Reserved.
a. Amyotrophic Lateral Sclerosis and the usefulness (or not) of the SOD1G93A mouse as an experimental model system
b. The importance of thorough, scientific characterization of experimental model systems
c. The importance of including behavioral assays in determining pathological processes
What are we going to discuss?
Ron Oppenheim
James Caress
Tom Hampton
David Gifondorwa
Mac RobinsonAnna Taylor
David Prevette
Thomas Gould
Ramon Jimenez-Moreno
Sherry Vinsant
Carol Mansfield
Jane Strupe
Phonepasong Arounleut
Masaaki Yoshikawa
Vickie Moore
Acknowledgements
Funding:
Wake Forest Brian White Funds
Blazeman Foundation for ALS
NIH/NINDS R01NS069212
NIH/NINDS R01NS036081
Robert Packard Center for ALS Research at Johns Hopkins
Collaborators and Colleagues:
350,000 individuals in the world have ALS/MND
120,000 diagnosed each year - 100,000 will die each year
30,000 individuals in US affected with 5000 new cases each year.
The ALS center at WFUBMC sees approximately 150 patients/year.
Adult onset (+ 55 years)
5-10% of cases are familial (fALS) with remaining 90-95% being sporadic (sALS).
Amyotrophic Lateral Sclerosis (ALS) Motor Neuron Disease (MND)
http://keribstill.com/
Amyotrophic Lateral Sclerosis (ALS) Motor Neuron Disease (MND)
Patients present with difficulties with:
• speech and swallowing
• muscle weakness and atrophy (loss of large motoneurons of brainstem and spinal cord)
• muscle fasciculations/twitching
• hyperreflexia and/or spasticity (lesions to upper motoneurons)
Intellect, cardiovascular and other body functions are not affected.
With no substantially effective treatment, patients die on average thee years after diagnosis.
http://keribstill.com/
90% sporadic
Variations in DCTN1 (dynactin 1), NEFH (neurofilament, heavy polypeptide), PRPH (peripherin) and SMN1 (survival motor neuron 1) increase chances of developing ALS.
ALS Patients and Genetics
ALS Patients and Genetics
10% familial
C9orf72 – 30-40% sALS- normal gene has a GGGGCC stretch, in ALS patients this can be repeated > 30 times
SOD1 – 20% - Superoxide Dismutase 1- mutation appears to be toxic gain of function
TARDBP (TDP-43) - 5% - TAR DNA binding protein, binds to RNA and ensures stability
FUS – 5% - fused in sarcoma – binds DNA and regulates transcription
ANG – 1% - angiogenin, ribonuclease involved in angiogenesis
ALS2, SeTX, VAPB
• Autosomal dominant missense point mutation in SOD1 identified in a subset of familial ALS patients (Rosen et al., 1993. Nature. 362(6415):59-62).
• 10-15% of familial ALS cases (1% of all cases) possess mutations in Cu+2/Zn+2 superoxide dismutase (SOD).
• Cu+2/Zn+2 SOD1 catalyzes the conversion of .O2 to O2 and H2O2.
• Mutation is toxic “gain of function”
• Cytoplasmic superoxide dismutase
• Mutation suggest a role for free radical damage in ALS.
Genetics and ALS?
• Gurney et al., 1994. Science 264(5166):1772-5
• Commercially available from Jackson Laboratory
• Females do not breed
• Autosomal dominant
• Develop “symptoms” at about 90 days
• Age of symptom onset is determined when mice can not fully extend legs.
• Die by about 120-140 days
G93AG93A mutant SOD1 mouse
Wild-Type
The SOD1G93A mouse model of ALS has been used in many pre-clinical studies.
a, Average age of symptom onset is significantly delayed in rhHsp70 injected animals (n = 7) compared with Riluzole treated (n = 12) and untreated mice (n = 11; ***p ≤ 0.001).
Gifondorwa DJ, et. al. Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 2007 Nov 28;27(48):13173-80.
SOD1 mice exhibit denervation of the neuromuscular junction (NMJ).
a, Injection of rhHsp70 resulted in an increased percentage of innervated NMJs in the MG at P90.
Gifondorwa DJ, et. al. Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 2007 Nov 28;27(48):13173-80.
Motoneurons die by endstage in the SOD1G93A mouse.
Vinsant S et al., (2013). Brain and Behavior 3 (4): 335–350. PMCID: PMC3869677 Vinsant S et al., (2013). Brain and Behavior 3 (4): 431–457. PMCID: PMC3869683 Modified from
Tradi onalcoun ngdoesnotreveallossofMNsun lendstage.
ButthenumberofvacuolatedMNspredictsMNsthatwilldegenerate.
• Charcot J-M (1874). De la sclérose latérale amyotrophique. Prog Med. 2: 325-327, 341-342, 453-455.
• Duchen LW, Strich SJ (1968). An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant ‘wobbler.’ J. Neurol Neurosurg Psychiatry 31 (6): 535-42)
• Messer, A., and Flaherty, L. (1986). Autosomal dominance in a late onset motor neuron disease in the mouse. J. Neurogenet 3: 345-355.
• Gurney ME, Pu H, Chiu AY, Dal Cnato MC et al., (1994). Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264(5166):1772-5.
• Wegorzewska I, Bell S, Cairns NJ, Miller TM, Baloh RH (2009). TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. PNAS 106(44): 18809-14.
Landmark papers in ALS
• Charcot J-M (1874). De la sclérose latérale amyotrophique. Prog Med. 2: 325-327, 341-342, 453-455.
• Duchen LW, Strich SJ (1968). An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant ‘wobbler.’ J. Neurol Neurosurg Psychiatry 31 (6): 535-42)
• Messer, A., and Flaherty, L. (1986). Autosomal dominance in a late onset motor neuron disease in the mouse. J. Neurogenet 3: 345-355.
• Gurney ME, Pu H, Chiu AY, Dal Cnato MC et al., (1994). Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264(5166):1772-5.
• Wegorzewska I, Bell S, Cairns NJ, Miller TM, Baloh RH (2009). TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. PNAS 106(44): 18809-14.
Title…
When and where does ALS pathology begin?
What cells and processes are involved?
SOD1G93A High Expression Chronology of Pathophysiology
• MNs are hyperexcitable (Pieri 2003; Kuo 2004; De Vos 2007)• Transient behavioral deficits (Van Zundert 2008; Saxena 2009)• Golgi fragmentation, mitochondrial vacuolization and damage
(Bendotti 2001; Gould 2006; Martin 2007)• ER stress (Saxena 2009)
• SOD1 aggregates (Johnston 2000; Turner 2003; Gould 2006)• Reduced motor units and muscle denervation (Frey 2000; Pun 2006; Gould 2006;
Hegedus 2007)• Axonal transport deficits (Ligon 2005)• Motor deficits (Open field test, grip strength (Barneoud 1997; Ligon 2005; Wooley
2005;Haywoth 2009)• Reduced numbers of spinal motoneurons, corticospinal and bulbar spinal neurons
(Zang 2002; Shin 2007; Martin 2007)• Disrupted BBB (Zhong 2008)
• Glial activation (Gould 2006)• VR and DR axon loss (Fischer 2004; Fischer 2005)• Hindlimb tremor (Chiu 1995)
• Rotorod deficits (Fischer 2005)• MN cell death (Chiu 1995; Gould 2006)
Progressive paralysis, loss of 50% MNs and death
P30
Birth
P60
P90
P120-endstage
Pre
-sym
pto
ma
tic
?
Pre
-sym
pto
ma
tic
rhHsp70 treatment delays symptom onset in G93A mice
Gifondorwa DJ, et. al. Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 2007 Nov 28;27(48):13173-80.
• Treatment beginning at postnatal day (P) 50 with rhHsp70 significantly delayed symptom onset and extended survival
• Treatment beginning at P90 had no effect on symptom onset or survival.
• Treatment beginning at P30 had greatest effects on extending survival.
wt
Bax
KO
SOD
1
SOD
/ B
ax K
O1
P140 end‐ stage
Dissociation of Motoneuron Death from ALS
• Loss or pro-apoptotic protein Bax prevents loss of MN during normal development
• Loss of Bax in the SOD1 mouse prevents MN cell death
• However, while there was a slight extension of survival, the BAX deficient SOD1 mice still died.
• Denervation of NMJ still occurs and in SOD1 mice, denervation occurs quite early.
When and where is earliest pathology?
Vinsant S et al., (2013). Brain and Behavior 3 (4): 335–350. PMCID: PMC3869677 Vinsant S et al., (2013). Brain and Behavior 3 (4): 431–457. PMCID: PMC3869683
When and where is earliest pathology?
Tibialis Anterior (TA)
• Anterior (skin)- Type 2B muscle fibers• Posterior (bone)- Type 2A, B , x muscle fibers• Motoneurons that innervate type 2B fibers are
most susceptible in ALS/MND.
Soleus
• Type 1 muscle fibers• Motoneurons that innervate type 1
fibers are less susceptible in ALS/MND.
Initial denervation of TA NMJs begins after postnatal day 14 and before day 30
Vinsant S et al., (2013). Brain and Behavior 3 (4): 335–350. PMCID: PMC3869677 Vinsant S et al., (2013). Brain and Behavior 3 (4): 431–457. PMCID: PMC3869683
Abnormalities are observed in the MN soma in region of the TA motor pool at P30
Wild Type
Wild Type
SOD+
SOD+
• Enlarged and vacuolated mitochondria are observed
• Clear, empty cytoplastmicvacuoles are present
P30 distal dendrites show more profound changes.
• Large, vacuolated mitochondria are prominent
• Clear, empty cytoplasmic vacuoles are also present in distal dendrites
• Distal dendrites are where many excitatory synapses are found on MNs
Fewer but larger mitochondria are observed in motoneuron soma at postnatal day 30.
Vinsant S et al., (2013). Brain and Behavior 3 (4): 335–350. PMCID: PMC3869677 Vinsant S et al., (2013). Brain and Behavior 3 (4): 431–457. PMCID: PMC3869683
Mitochondria membrane potential, ATP content and generation are reduced in SODG93A at day 30.
Vinsant S et al., (2013). Brain and Behavior 3 (4): 335–350. PMCID: PMC3869677 Vinsant S et al., (2013). Brain and Behavior 3 (4): 431–457. PMCID: PMC3869683
Wild type
SODG93A SODG93A
Mitochondrial abnormali es are seen in axons in TA and occasionally in soleus at P30.
TA soleus
SOD1 SOD1
WT
Abnormal mitochondria are observed in axons at day 30.
Mitochondria morphological alterations are also observed in motoneuron terminals in NMJs of TA and soleus muscles.
SOD1 WT
Mitochondria morphological alterations are also observed in motoneuron terminals in NMJs of TA and soleus muscles.
SOD1 WT
Fewer but larger mitochondria are observed presynaptic terminals in both TA and soleus NMJs.
• Using ultrastuctural characteristics, the number and type of afferent synapses was determined at day 30.
• A C-type synapse that is usually excitatory is shown in A.
• A type 2 synapse that is usually inhibitory is shown in B.
• A type 1 synapse that is usually excitatory is shown in C.
• In the SOD1 animals, synaptic morphologies appeared normal.
Are there other indicators of pathology at day 30?
Wild Type
SOD1
• There is a decrease in the number of excitatory, Type 1 synapses on the MN cell body.
• There is an increase in the number of C-type synapses on the MN cell body.
• This is also a decrease in the number of excitatory, Type 1 synapses on distal dendrites.
The number and type of afferent synapses is altered at day 30.
Axo-somatic synapses
Axo-dendritic synapses
• Mitochondrial abnormalities are abundant in dendrites, soma and NMJ presynaptic terminal.
• Mitochondria membrane potential, ATP content and generation are reduced in lumbar spinal cord.
• Small, empty cytoplasmic vacuoles appear in motoneuron soma and dendrites.
• Decrease in total synapse and excitatory synapses in distal dendrites
• No change in total number of synapses, but decrease in excitatory and increase in C-terminals
• Denervation of tibialis anterior and medial gastrocnemius muscles
• No apparent change in retrograde transport.
By postnatal day 30 there are obvious pathological changes observed in the SOD1 mouse.
Symptom onset in the SOD1 mouse occurs much later than day 30.
Gifondorwa DJ, et. al. Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 2007 Nov 28;27(48):13173-80.
G93A
Wild-Type
P90
Age of symptom onset was determined when mice can not fully extend legs.
Observed typically day 90
The initial symptoms of ALS can be quite varied in different people. One person may have trouble grasping a pen or lifting a coffee cup, while another person may experience a change in vocal pitch when speaking. ALS is typically a disease that involves a gradual onset.
http://www.alsa.org/about-als/symptoms
Jon “the Blazeman” Blais (www.waronals.org)
He noticed he was having a hard time holding things -- soap, toothbrush, etc. -- but he kept putting off seeing someone about it.
Digigait Imaging System Mouse Specific
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We wanted to determine of the pathological changes were associated with symptom onset.
Digigait Imaging System Mouse Specific
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Mouse Specific
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Gait dynamics were recorded using ventral plane videography using the Digigait Imaging System.
Decreases in limb stance width and increases in variability of paw placement angle occur at the time of initial denervation
Forelimb stance width
Hindlimb stance width
• In mouse models, pathological changes occur much earlier than overt behavior changes.
• It is essential to characterize early pathology and utilize appropriate behavioral analysis.
• By understanding the earliest pathology, we will
- gain insight into potential causes of disease,
- identify biomarkers, and
- develop effective therapeutics
Conclusions…
Changes in DigiGait measures in a progressive animal model of Parkinson's disease
Charles K. Meshul, Ph.D
Research Biologist, VA Medical Center/Portland and Professor,
Department of Behavioral Neuroscience
Oregon Health & Science University
Copyright 2015 C.K.Meshul, Mouse Specifics Inc. & InsideScientific. All Rights Reserved.
Acknowledgments
The important contributions from the following individuals are greatly appreciated:
Michelle Sconce
Madeline Churchill
Rebecca Hood
Natalie Goldberg
This research was supported by the Department of Veterans Affairs Merit Review Program
The Parkinson’s disease (PD) animal model
• Most PD rodent models primarily have used acute/subacute toxin administration, resulting in >70-95% unilateral or bilateral loss of nigrostriatal dopamine. This results in significant motor dysfunction.
• We have used a progressive loss of dopamine over a 4-week time period to try and simulate the longer term loss of dopamine as seen in PD patients. This results in a 60-80% loss of dopamine. This slower loss of dopamine most likely results in the brain adapting to the new environment, making motor dysfunction more difficult to measure.
• Most treatment paradigms have used a neuroprotection strategy, which are not clinically relevant. We have tested treatments either during (intervention) or following (restoration) progressive MPTP administration.
Dopaminergic and Behavioral Correlations
• Increased dosing of MPTP over a 4-week time period results in a progressive loss of dopamine.
• Treatment can be initiated anytime during this 4-week time period, although the emphasis in terms of translation is more in restoration versus protection.
Goldberg et al: Dopaminergic and Behavioral Correlates of Progressive Lesioning of the Nigrostriatal Pathway with 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine. Neuroscience 180:256-271 (2011).
Gait dynamics in vehicle and MPTP-treated (4mg/kg – 32 mg/kg) at a walking speed of 24 cm/s
Goldberg et al.: Profiling changes in gait dynamics resulting from progressive MPTP-induced nigrostriatal lesioning. J. Neuroscience Research 89:1698-1706 (2011).
Sconce et al: Intervention with 7,8-dihydroxyflavone blocks further striatal terminal loss and restores motor deficits in a progressive mouse model of Parkinson’s disease. Neuroscience 290:454-471 (2015).
Intervention with 7,8-dihydroxyflavone (DHF): Gait changes
With MPTP treatment, the forepaws exerted a greater
distance from the midline compared to the
hindpaws (ie negative values).
Correlation of dopamine, sprouting and second messengerbiomarkers on measures of motor function
• With a decrease in TH/dopamine terminals within the striatum following MPTP treatment, there was an increase in the time that the hind paws were on the belt during running. There was improvement following DHF treatment.
• Following DHF treatment, there was an increase in the levels of SCG 10 (sprouting factor) and the activated BDNF receptor (pTrkB), resulting in gait symmetry between the forepaws and hindpaws.
Sconce et al: Intervention with 7,8-dihydroxyflavone blocks further striatal terminal loss and restores motor deficits in a progressive mouse model of Parkinson’s disease. Neuroscience 290:454-471 (2015)..
Intervention with Exercise
• Progressive treatment with MPTP results in changes in several measures of gait, including paw area, stance width and shared stance, suggesting instability due to dopamine loss.
• Intervention with voluntary exercise, starting 2 weeks after the start of MPTP treatment, results in recovery of these gait measures.
Sconce et al: Intervention with exercise restores motor deficits but not nigrostriatal loss in a progressive MPTP mouse model of Parkinson’s disease. Neuroscience 299:156-174 (2015).
Maximal rate of change of paw
area in contact with belt during
breaking phase.
% of stance of hind paws in contact
with belt at same time.
• With MPTP treatment, levels of the glutamate transporter increased, which was positively correlated with an increase in paw area.
• Interestingly, as the levels of the vesicular dopamine transporter, VMAT2, decreased, the paw area increased.
Correlation of dopamine and glutamate biomarkers
Curcumin Treatment Improves Motor Behavior in ɑ-Synuclein Transgenic Mice
Spinelli et al: Curcumin treatment improves motor behavior in alpha-synulcein transgenic mice. Plos One, 10(6): e0128510 (2015).
MPTP: 4 weeks, followed by DHF treatment for 4 weeks (restoration). Most of the DigiGait measures were significantly different 4 weeks after MPTP treatment (MPTP group)compared to the 4wk MPTP only group.
Flavone-induced restoration of gait function following MPTP
Sconce et al: in preparation
• MPTP treatment resulted in increased stance width, decreased stance/swing, increased swing time, and increased paw angle.
• The changes in gait described above were reversed following DHF treatment and these were correlated with changes in second messenger and sprouting levels.
Correlation of sprouting and second messenger biomarkers with gait measures following flavone treatment.
Sconce et al: in preparation
Data courtesy of: Madeline Churchill (manuscript in preparation)
• 4 weeks of MPTP followed by 4 weeks of daily cyclosporin A treatment (restoration)• Greater stance width implies overcompensation for gait instability; connected with step angle variance.
Effect of Cyclosporin A (CsA) treatment following MPTP
Blue bars = CsA treatmentWhite bars = vehicle treatment
Summary & Conclusions
1. Progressive loss of dopamine in a mouse model of PD, followed by withdrawal of the toxin for 1-4 weeks, results in variable changes in several measures of gait. All the MPTP-induced gait alterations appear to be connected to gait instability. However, the slight differences in dopamine loss (60-75%) may contribute to which gait measures are affected.
2. Although the same strain of mouse (male, C57Bl/6J, 12-15 weeks old) and dose of MPTP are used for each study, the variability in the differences in gait measures may simply replicate what is seen in patients with PD. Not all PD patients develop exactly the identical motor disturbances. Our data may be reflective of those differences seen in the human population despite the fact that the same strain/sex/age of mouse is used.
Thank You!For additional information on Mouse Specifics equipment specially designed for gait analysis in rodents please visit:
https://mousespecifics.com/