Activity of Monoamine Oxidase in the Nigrostriatal System at Presymptomatic and Early Symptomatic Stages of Parkinsonism in Mice

Khakimova, G. R.; Козина, Е. А.; Buneeva, O. A.; Aksenova, L N; Медведев, А. Е.; Ugryumov, M. V.

doi:10.1007/s10517-015-2990-x

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…It has been well established that age accounts for different responses in parkin-null rodents and that parkin knockout models compensate better for the lack of parkin protein than parkin mutant models 8 . Moreover, activity of MAO-B in the striatum is decreased in mouse model of pre-symptomatic PD (~59% loss of DAergic axons) and returns to the control levels during symptomatic stage, whereas activity of MAO-A is unchanged in the pre-symptomatic PD model and augmented in the symptomatic PD 13 . Our data is consistent with these findings, suggesting that the 2 month-old male PKO rats may represent a very early stage of PD, manifested by deficit in MAO-B function and increased ß-PEA levels, at which the nigrostriatal system still is able to compensate for consequences of parkin loss of function.…”

Section: Discussionmentioning

confidence: 96%

Characterization of Dopaminergic System in the Striatum of Young Adult Park2−/− Knockout Rats

Gemechu

Sharma

et al. 2018

Sci Rep

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Mutations in parkin gene (Park2) are linked to early-onset autosomal recessive Parkinson’s disease (PD) and young-onset sporadic PD. Park2 knockout (PKO) rodents; however, do not display neurodegeneration of the nigrostriatal pathway, suggesting age-dependent compensatory changes. Our goal was to examine dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to characterize compensatory mechanisms that may have occurred within the system. The striata form wild type (WT) and PKO Long Evans male rats were assessed for the levels of DAergic markers, for monoamine oxidase (MAO) A and B activities and levels, and for the levels of their respective preferred substrates, serotonin (5-HT) and ß-phenylethylamine (ß-PEA). The PKO rats displayed lower activities of MAOs and higher levels of ß-PEA in the striatum than their WT counterparts. Decreased levels of ß-PEA receptor, trace amine-associated receptor 1 (TAAR-1), and postsynaptic DA D2 (D2L) receptor accompanied these alterations. Drug-naive PKO rats displayed normal locomotor activity; however, they displayed decreased locomotor response to a low dose of psychostimulant methamphetamine, suggesting altered DAergic neurotransmission in the striatum when challenged with an indirect agonist. Altogether, our findings suggest that 2 month-old PKO male rats have altered DAergic and trace aminergic signaling.

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Section: Discussionmentioning

confidence: 96%

Characterization of Dopaminergic System in the Striatum of Young Adult Park2−/− Knockout Rats

Gemechu

Sharma

et al. 2018

Sci Rep

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“…Thus, the frequency of neuron activity is high and accompanied by high metabolism. In addition, dopaminergic neurons in the midbrain express high monoamine oxidase, which can produce many oxygen-free radicals that cause neuron damage [46]. In this study, we excluded the effect of other brain regions on the pathological formation of the SNc by only infecting SNc neurons, which is important in determining the effect of independent expression of α-syn in the SNc on the pathological formation of PD.…”

Section: Neural Plasticitymentioning

confidence: 99%

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging

et al. 2020

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The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKβ-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD.

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Cholinergic and Dopaminergic Alterations in Nigrostriatal Neurons Are Involved in Environmental Enrichment Motor Protection in a Mouse Model of Parkinson’s Disease

et al. 2016

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Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, being characterized by dopaminergic neurodegeneration of substantia nigra pars compacta. PD pharmacotherapy has been based on dopamine replacement in the striatum with the dopaminergic precursor 3,4-dihydroxyphenylalanine (L-DOPA) and/or with dopaminergic agonists, alongside anticholinergic drugs in order to mitigate the motor abnormalities. However, these practices neither prevent nor stop the progression of the disease. Environmental enrichment (EE) has effectively prevented several neurodegenerative processes, mainly in preclinical trials. Several studies have demonstrated that EE induces biological changes, bearing on cognitive enhancement, neuroprotection, and on the attenuation of the effects of stress, anxiety, and depression. Herein, we investigated whether EE could prevent the motor, biochemical, and molecular abnormalities in a murine model of PD induced by 1-methyl-4-phenyl-2,3-dihydropyridine (MPTP). Our results show that EE does not prevent the dopaminergic striatal depletion induced by MPTP, despite having averted the MPTP-induced hyperlocomotion. However, it was able to slow down and avoid, respectively, the 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion. Analysis of dopaminergic mRNA alterations in the midbrain showed that D1R expression was increased by MPTP, while the normal expression level of this receptor was restored by EE. As for the cholinergic system, MPTP led to a decrease in the ChAT gene expression while increasing the expression of both AChE and M1R. EE attenuated and prevented-respectively-ChAT and M1R gene expression alterations triggered by MPTP in the midbrain. Overall, our data brings new evidence supporting the neuroprotective potential of EE in PD, focusing on the interaction between dopaminergic and cholinergic systems.

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Activity of Monoamine Oxidase in the Nigrostriatal System at Presymptomatic and Early Symptomatic Stages of Parkinsonism in Mice

Cited by 5 publications

References 11 publications

Characterization of Dopaminergic System in the Striatum of Young Adult Park2−/− Knockout Rats

Characterization of Dopaminergic System in the Striatum of Young Adult Park2−/− Knockout Rats

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging

Cholinergic and Dopaminergic Alterations in Nigrostriatal Neurons Are Involved in Environmental Enrichment Motor Protection in a Mouse Model of Parkinson’s Disease

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