Automated quantitative gait analysis in animal models of movement disorders

Vandeputte, Caroline; Taymans, Jean-Marc; Casteels, Cindy; Coun, Frea; Ni, Yicheng; Laere, Koen Van; Baekelandt, Veerle

doi:10.1186/1471-2202-11-92

Cited by 143 publications

(129 citation statements)

References 39 publications

(49 reference statements)

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“…27 In the present study, we used CatWalk because this is more sensitive in measuring gait deficits in some animals than the rotarod test. 28 Using CatWalk, we found that chronically hyponatremic rats displayed findings similar to those seen in Purkinje cell-specific vesicular g-aminobutyric acid transporter knockout 29 or atm-deficient mice, 30 which exhibit cerebellar ataxia. The mechanisms underlying hyponatremia-induced gait abnormalities are currently unknown.…”

Section: Discussionmentioning

confidence: 79%

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Fujisawa

Sugimura

Takagi

et al. 2016

Journal of the American Society of Nephrology

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Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.

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Section: Discussionmentioning

confidence: 79%

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Fujisawa

Sugimura

Takagi

et al. 2016

Journal of the American Society of Nephrology

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“…Here, we show that combination of memantine with rtPA is associated with better sensorimotor status (string test) and use of the plantar surface of the ipsilateral hind limb (CatWalk), a parameter also impaired in other cortical infarct models. 25 Memantine, as an individual treatment, is not effective in our thrombotic stroke model. These data are in agreement with the literature, because any beneficial effect of memantine alone was reported on a stroke model performed in healthy adult mice or rats when administrated after stroke onset.…”

Section: Discussionmentioning

confidence: 88%

“…The maximum contact area spatial parameter (ie, the maximum area of a paw in contact with the glass plate during the stance phase) was used as a measure of individual paw prints, as previously described. 25 The size of the right hind limb print was reduced (Ϫ27%) in delayed reperfused animals ( Figure 4A; saline versus late rtPA; PϽ0.05), whereas memantine alone did not improve the deficit measured in saline animals ( Figure 4A; saline versus late memantine; PϾ0.05). The coinjection of memantine with rtPA prevented the deleterious effects of late thrombolysis ( Figure 4A; late rtPA versus late memantine/rtPA; Pϭ0.05 and saline versus late memantine/ rtPA; PϾ0.05).…”

Section: Memantine Precludes the Deleterious Effects Of Delayed Thrommentioning

confidence: 97%

Memantine Improves Safety of Thrombolysis for Stroke

Montagne

Hébert

Jullienne

et al. 2012

Stroke

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Background and Purpose-Despite side effects including N-methyl-D-aspartate-mediated neurotoxicity, recombinant tissue-type plasminogen activator (rtPA) remains the only approved acute treatment for ischemic stroke. Memantine, used for treatment of Alzheimer disease, is an antagonist for N-methyl-D-aspartate receptors. We investigated whether memantine could be used as a neuroprotective adjunct therapy for rtPA-induced thrombolysis after stroke. Methods-In vitro N-methyl-D-aspartate exposure, oxygen and glucose deprivation, and N-methyl-D-aspartate-mediated calcium videomicroscopy experiments were performed on murine cortical neurons in the presence of rtPA and memantine. The therapeutic safety of rtPA and memantine coadministration was evaluated in mouse models of thrombotic stroke and intracerebral hemorrhage. Ischemic and hemorrhagic volumes were assessed by MRI and neurological evaluation was performed by the string test and automated gait analysis. Results-Our in vitro observations showed that memantine was able to prevent the proneurotoxic effects of rtPA in cultured cortical neurons. Although memantine did not alter the fibrinolytic activity of rtPA, our in vivo observations revealed that it blunted the noxious effects of delayed thrombolysis on lesion volumes and neurological deficits after ischemic stroke. In addition, memantine rescued rtPA-induced decrease in survival rate after intracerebral hemorrhage. Conclusions-Memantine could be used as an adjunct therapy to improve the safety of thrombolysis.

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“…Each mouse was allowed three attempts to hold onto the inverted lid for an arbitrary maximum of 90 s, and the longest time was recorded. To evaluate motor coordination, we analyzed stride length for 14-wk-old mice with the use of a CatWalk apparatus (Noldus) (31). Each mouse was placed individually on the CatWalk walkway and allowed to traverse the glass plate of the walkway as many times as needed to obtain at least three fluent crossings in the dark.…”

Section: Methodsmentioning

confidence: 99%

MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS

Lee¹,

Shin²,

Hwang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Dominant mutations in the gene for superoxide dismutase 1 (SOD1) give rise to familial ALS by an unknown mechanism. Here we show that genetic deficiency of mammalian sterile 20-like kinase 1 (MST1) delays disease onset and extends survival in mice expressing the ALS-associated G93A mutant of human SOD1. SOD1(G93A) induces dissociation of MST1 from a redox protein thioredoxin-1 and promotes MST1 activation in spinal cord neurons in a reactive oxygen species-dependent manner. Moreover, MST1 was found to mediate SOD1(G93A)-induced activation of p38 mitogen-activated protein kinase and caspases as well as impairment of autophagy in spinal cord motoneurons of SOD1(G93A) mice. Our findings implicate MST1 as a key determinant of neurodegeneration in ALS.neurotoxicity | ROS A myotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons in the brain and spinal cord. Whereas most cases (∼90%) of ALS are sporadic (sALS), both sALS and familial ALS (fALS) share similar clinical characteristics, suggestive of common disease mechanisms. Mutations in the gene for superoxide dismutase 1 (SOD1) are one of the most common causes of fALS and give rise to disease as a result of acquired gain-offunction toxicity (1, 2). Studies using the disease-model mice overexpressing ALS-linked mutants of human SOD1 have suggested that many mutations result in oxidative damage and apoptosis in motor neurons (2, 3). The molecular mechanism by which SOD1 mutants induce neurodegeneration remains unclear, however.Mammalian sterile 20 (STE20)-like kinase 1 (MST1) is a multifunctional serine-threonine kinase that belongs to the family of class II germinal center kinases (4-6). MST1 is composed of a catalytic domain in the amino-terminal region, an inhibitory domain in the central region, and a regulatory Salvador/ Rassf/Hippo (SARAH) domain in the carboxyl-terminal region (7,8). The SARAH domain is responsible for the homo-dimerization of MST1, which contributes to the mechanism underlying MST1 activation (7, 9). It also mediates the formation of heteromeric complexes with other SARAH domain-containing proteins such as 45 kDa WW domain protein and Rassf proteins (7,8). MST1 is expressed ubiquitously and is associated with the regulatory mechanisms for many biological events including cell growth, apoptosis, stress response, and senescence (10, 11). In particular, MST1 has been recently suggested to mediate neuronal cell death initiated by oxidative stress (11,12).Given that oxidative stress contributes to the pathogenesis of ALS, we investigated the possible role of MST1 in the neurotoxicity underlying fALS with use of a transgenic mouse model. Results and DiscussionMotor Neurons in sALS Patients and SOD1(G93A) Mice Show Higher Activity of MST1. We first examined MST1 activity in primary motor neurons (PMNs) prepared from the spinal cord of E13 embryos of contro...

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Automated quantitative gait analysis in animal models of movement disorders

Cited by 143 publications

References 39 publications

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Memantine Improves Safety of Thrombolysis for Stroke

MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS

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