Effects of fibroblast growth factors on MPTP-induced parkinsonian syndrome in mice

Kryzhanovsky, G. N.; Kucheryanu, V. G.; Pozdnyakov, O. M.; Kladkevich, E.B.; Krupina, N. A.; Nikushkin, E. V.; Osuga, Yutaka

doi:10.1016/s0928-4680(96)00160-5

Cited by 13 publications

(6 citation statements)

References 53 publications

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“…Firstly, hypokinesia was assessed by quantifying "open field" spontaneous locomotor activity based on previous methodologies but in response to MPTP treatment as a prototypic drug [29] and [30] for a period of 0-6 min after 5 min acclimatization in an animal activity meter (Opto-Variomex-3 Auto-Track system, Columbus Instruments, Columbus, Ohio, USA). The 0-6 min recording time was chosen since it represented an optimal period for detecting neurotoxin-induced locomotor hypokinesia in 3-minute intervals up to a total of 30 minutes in C57Bl/6 mice [27] and [31]. Additionally, total locomotor distance, cumulative ambulation time as well as speed (horizontal activity measures) and vertical rearing (vertical activity measure) as well as immobility time were recorded.…”

Section: Behavioural Testsmentioning

confidence: 99%

Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms

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Давыдова

Narkevich

et al. 2015

Behavioural Brain Research

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Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay. Levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected using HPLC with electrochemical detection in the substantia nigra (SN) and striatum. The oligomers or fibrils administered alone or in a 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behaviour was tested on days 0, 15 and 28 of the protocol, at which time brain structures were sampled. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e. 14 days after treatment completion) induced hypokinesia and immobility whilst the aggregate combination additionally produced rigidity. The α-Syn oligomer/fibril mixture also instigated PD-like motor symptoms which correlated heterochronically with elevated NA levels in the striatum but then later in the SN while intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations throughout the protocol. In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Neurodegenerative and/or actions on neurotransmitter transporters (such as NET, SERT and VMAT2) are discussed as being implicated in these α-syn amyloid induced neurochemical and motoric disturbances.

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Section: Behavioural Testsmentioning

confidence: 99%

Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms

Gruden

Давыдова

Narkevich

et al. 2015

Behavioural Brain Research

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“…The 0-6 min recording time was chosen since it represented an optimal period for detecting neurotoxininduced locomotor hypokinesia in 3-minute intervals up to a total of 30 minutes in C57Bl/6 mice [15,19] Additionally, total locomotor distance, cumulative ambulation time as well as speed (horizontal activity measures) and vertical rearing (vertical activity measure) as well as immobility time were recorded. Secondly, muscle rigidity was gauged using a "gibbosity" test manifested by the shortening of the neck to the tailbase measurement and scored by the following scoring scale: (0) = no rigidity; (1) = 1.0cm decrease; (2) = 2.0cm decrease; (3) = >2.0cm decrease [15].…”

Section: Behavioural Testsmentioning

confidence: 99%

Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates

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Давыдова

Narkevich

et al. 2014

Behavioural Brain Research

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Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with α-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries. In vitro generated α-syn oligomers and fibrils were characterized using atomic force microscopy and the thioflavin T binding assay. These toxic oligomers or fibrils administered alone (0.48 mg/kg) or their 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behavior was tested on days 0, 15 and 28 of the protocol. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e., 14 days after treatment completion) induced rigidity, hypokinesia and immobility. This was accompanied by elevated nigral but not striatal DA, DOPAC and HVA concentrations in response to dual administration of α-syn oligomers plus fibrils but not the oligomers by themselves. α-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the substantia nigra. Only nigral DA turnover (DOPAC/DA but not HVA/DA ratio) was augmented in response to fibril treatment but there were no changes in the striatum. Compilation of these novel behavioral and neurochemical findings substantiate the validity of the α-syn nasal vector model for investigating parkinsonian-like symptoms.

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“…Locomotor activity of animals in the open-fi eld test was studied using an Opto-Varimex-3 system (Columbus Instruments). The total length of the track, time of immobility, and number of vertical rearing postures were measured over 3 min [5]. The step length was estimated when the animal moved along a straight line [8].…”

Section: Methodsmentioning

confidence: 99%

Experimental modeling of preclinical and clinical stages of Parkinson’s disease

et al. 2011

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Degeneration of dopaminergic (DAergic) neurons of the nigrostriatal system is the key stage in the pathogenesis of Parkinson's disease. The first symptoms of this disease are observed after degeneration of 70-80% neurons, which occurs over 20-30 years. The clinical stage of Parkinson's disease begins after this period. Late diagnostics of Parkinson's disease contributes to low efficiency of therapy for this disorder. Detailed study of the pathogenesis and development of preclinical diagnostic methods for Parkinson's disease are the urgent problems. This work was designed to develop a new experimental model of the preclinical and clinical stages of the disease. Experimental modeling was performed on C57Bl/6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This agent is converted into the MPP(+)-neurotoxin in brain DAergic neurons. We showed that MPTP in a dose of 4 mg/kg has no effect on the nigrostriatal DAergic system. MPTP in a dose of 8-16 mg/kg produced the toxic effect only on DAergic axons, which simulates the preclinical stage of Parkinson's disease. MPTP in a dose of 20-40 mg/kg had the toxic effect on neuronal axons and bodies, which simulates the clinical stage of Parkinson's disease. The data suggest that progressive degeneration of DAergic neurons is accompanied by activation of compensatory mechanisms for functional deficiency of these cells.

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Effects of fibroblast growth factors on MPTP-induced parkinsonian syndrome in mice

Cited by 13 publications

References 53 publications

Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms

Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms

Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates

Experimental modeling of preclinical and clinical stages of Parkinson’s disease

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