Modeling of presymptomatic and symptomatic stages of parkinsonism in mice

Ugrumov, M. V.; Khaindrava, V. G.; Козина, Е. А.; Kucheryanu, V. G.; Бочаров, Е. В.; Kryzhanovsky, G. N.; Кудрин, В. С.; Narkevich, V. B.; Клодт, П. М.; Rayevsky, K.S.; Pronina, T. S.

doi:10.1016/j.neuroscience.2011.03.007

Cited by 112 publications

(101 citation statements)

References 69 publications

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“…In the models of preclinical and clinical stages of PD, the dopamine level in the murine striatum was decreased by 57% and 80%, respectively ( Table ), in comparison to the control group; this finding almost completely coincides with the previously obtained data [22]. A 48% reduction in the total distance in the open-field test as compared to the control ( Table ) was found for the model of clinical stage of PD, which is similar to the motor dysfunctions observed in the previous study [22].…”

Section: Discussionsupporting

confidence: 90%

“…We previously demonstrated a 56% reduction in the dopamine level in the striatum in a model of advanced preclinical stage of PD using two injections of MPTP at a single dose of 12 mg/kg; in the early clinical stage model of PD (four injections of MPTP at the same single dose), the dopamine level decreased by 75% compared with the control [22]. The MPTP doses used in this study for PD modeling in mice purchased from the Pushchino animal facility are slightly different from those we described earlier for animals from the Stolbovaya facility [22].…”

Section: Discussionmentioning

confidence: 99%

“…The MPTP doses used in this study for PD modeling in mice purchased from the Pushchino animal facility are slightly different from those we described earlier for animals from the Stolbovaya facility [22]. It is known that mice of the same line but obtained from different facilities may differ in sensitivity to MPTP [23].…”

Section: Discussionmentioning

confidence: 99%

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Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

Kim¹,

Павленко²,

Катаргина³

et al. 2018

Acta Naturae

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Parkinson’s disease (PD) is a systemic neurodegenerative condition caused by the death of dopaminergic neurons of the nigrostriatal system of the brain. This disease is diagnosed after most neurons have already been lost, which explains the low efficiency of treatment. Hope for increasing treatment efficiency rests in the development of new strategies for early diagnosis of PD based on a search for peripheral markers that appear as early changes in non-motor functions. Since impairment of the visual function is one of the manifestations of PD, the purpose of our work was to identify biochemical and physiological changes in a mouse’s eye and eyelid in models of preclinical (presymptomatic) and clinical (symptomatic) stages of PD. We found that the norepinephrine, dopamine, and serotonin levels in the mouse eye reduced not only in the model of the early clinical stage, but also in the model of preclinical stage, an indication that pathological changes in the monoaminergic systems of the brain had affected the eye even before the motor disorders emerged. Moreover, in both models of PD, mice had increased intraocular pressure, indicating the development of both metabolic and functional impairments, which can be used as diagnostic markers. Unlike in the eye, the serotonin level in the eyelid was increased in mice at both parkinsonism stages and in presymptomatic mice to a much higher extent than in symptomatic ones. Given that serotonin is involved in the regulation of lacrimal glands of the eyelid, an increase in its level in parkinsonian mice should alter the composition of tear fluid, which could serve as a diagnostic marker of early stage of PD. Thus, the changes in the metabolism of monoamines in the eye and eyelid observed in mice at the early stage of parkinsonism are accompanied by changes in the function of these structures and, therefore, can be used as diagnostic markers of the early stage of PD.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

Kim¹,

Павленко²,

Катаргина³

et al. 2018

Acta Naturae

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“…This model is probably not completely adequate to study changes in gene expression. It is possible that future studies of other neurotoxic models, especially MPTP models, which reproduce presymptomatic and early symptomatic stages of PD [21], will allow the identification of genes and processes that are involved in the pathogenesis of the early stages of PD, and the investigation of compensatory mechanisms that will ensure long-term asymptomatic disease.…”

Section: Genementioning

confidence: 99%

Transcriptome profiling of 6-OHDA model of Parkinson’s disease

Шадрина¹,

Filatova

Alieva³

et al. 2013

ABB

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Analysis of monogenic forms and candidate genes of Parkinson's disease (PD) does not allow to describe completely the contribution of genetic factors to the etiopathogenesis of the disorder. An approach associated with an analysis of changes in a transcriptome pattern during the development of the disease in model objects can be used to identify new candidate genes that are involved in the pathogenesis of PD. In this work, we performed a transcriptome analysis of a PD model, created via stereotaxic unilateral introduction of the 6-hydroxidopamine (6-OHDA) into the substantia nigra pars compacta (SNpc) of a rat brain, to identify new candidate genes for PD. We studied transcriptome alterations in the substantia nigra of the rat brains 2 weeks after toxin administration, when the rats developed the Parkinson-like phenotype, and 4 weeks after toxin administration, when maximal changes in the behavior of animals were observed. The transcriptome analysis of the substantia nigra of the rat brains at the first time point (2 weeks) revealed changes in expression of genes that were clustered with high significance (p < 0.01, modified Fisher extract p value) into three metabolic pathways according to protein participation: modification of the extracellular matrix, signal transduction (including genes encoding signal peptides), and inflammation processes. This likely indicates that, during this time nonspecific effects associated with the response to surgery took place in the substantia nigra of the rats. Concomitantly, the situation changed dramatically and a response associated with damage to the nervous tissue was observed 4 weeks after neurotoxin administration. As a result, we identified five metabolic pathways containing predominantly genes, that encode protein products that are involved in the processes of neuron projection, normal functioning of the soma and dendrites of neurons, synaptic transmission, and transmission of nerve impulses (p < 0.01, modified Fisher extract p value).

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“…A species close to Ulomoides dermestoides is the beetle Alphitobius diaperinus, which is also used in folk medicine to treat various diseases, including one of the most socially important-Parkinson's disease. It was assumed that the Alphitobius diaperinus biomass homogenate may exhibit inhibitory activity with respect to MPTP (methylphenyl tetrahydropyri dine)-a toxin that causes experimental parkinsonism in C57BL/6JSto mice [12,13].…”

mentioning

confidence: 99%