Browsing by Subject "Parkinson’s disease"

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    A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity
    (MDPI, ) Cuenca, Lorena; Pizzichini, Elisa; Gonçalves, Valeria C.; Guillén Díaz, María; Aguilar Moñino, Elena; Sánchez Rodrigo, Consuelo; González Cuello, Ana María; Fernández Villalba, Emiliano; Herrero, María Trinidad; Enfermería
    The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100 were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.
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    Cardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys.
    (Wiley Online Library, 2019-11) Almela, Pilar; Cuenca Bermejo, Lorena; Yuste, José E.; Estrada, Cristina; Pablos, Vicente de; Bautista Hernández, Víctor; Fernández Villalba, Emiliano; Laorden, María Luisa; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
    ABSTRACT: Background: Autonomic dysfunction is a well-known dominant symptom in the advanced stages of Parkinson’s disease. However, the role of cardiac sympathetic nerves still needs to be elucidated. Objectives: To evaluate cardiac sympathetic response in Parkinsonian and dyskinetic monkeys. Methods: Adult male monkeys were divided into 1 of the following 3 groups: controls, 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine–treated monkeys, and 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine+levodopa–treated animals. Noradrenaline, its metabolite normetanephrine, and phospho-Heat shock proten 27 (p-Hsp27) at erine 82 levels were analyzed in the left and right ventricles of the heart. Tyrosine hydroxylase immunohistochemistry was performed in the ventral mesencephalon. Results: The results were the following: (1) 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine intoxication significantly increased normetanephrine levels and decreased noradrenaline turnover in the right ventricle without changes in the left ventricle; however, (2) levodopa treatment decreased noradrenaline levels and enhanced the normetanephrine/noradrenaline ratio in parallel with a very significant increase of Hsp27 activity in both ventricles. Conclusions: Levodopa treatment could induce protective cardiac effects through the increased Hsp27 activity. © 2019 International Parkinson and Movement Disorder Society
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    Electrical stimulation or MK-801 in the inferior colliculus improve motor deficits in MPTP-treated mice
    (Elsevier. Science Direct, 2018-01) Melo Thomas, L; Gil-Martinez, AL; Cuenca, L; Estrada, C; Gonzalez-Cuello, A; Schwarting, RK; Herrero, MT; Enfermería
    The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p < 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.
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    Fragmentation of the Golgi complex of dopaminergic neurons in human substantia nigra: New cytopathological findings in Parkinson's disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Tomás, Mónica; Martínez Alonso, Emma; Martínez Martínez, Narcisa; Cara Esteban, Mireia; Martínez Menárguez, José A.
    Fragmentation of the Golgi ribbon is a common feature of Parkinson’s disease and other neurodegenerative diseases. This alteration could be the consequence of the anterograde and retrograde transport imbalance, α-synuclein aggregates, and/or cytoskeleton alterations. Most information on this process has been obtained from cellular and animal experimental models, and as such, there is little information available on human tissue. If the information on human tissue was available, it may help to understand the cytopathological mechanisms of this disease. In the present study, we analyzed the morphological characteristics of the Golgi complex of dopaminergic neurons in human samples of substantia nigra of control and Parkinson’s disease patients. We measured the expression levels of putative molecules involved in Golgi fragmentation, including αsynuclein, tubulin, and Golgi-associated regulatory and structural proteins. We show that, as a consequence of the disease, the Golgi complex is fragmented into small stacks without vesiculation. We found that only a limited number of regulatory proteins are altered. Rab1, a small GTPase regulating endoplasmic reticulum-to-Golgi transport, is the most dramatically affected, being highly overexpressed in the surviving neurons. We found that the SNARE protein syntaxin 5 forms extracellular aggregates resembling the amyloid plaques characteristic of Alzheimer’s disease. These findings may help to understand the cytopathology of Parkinson’s disease.
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    Morphologic changes within the cerebellar cortex in the unilateral 6-hydroxydopamine lesioned rat model for Parkinson disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wu, Chenghua; Fan, Guoguang; Wu, Chunli; Yu, Guibo; Li, Zixuan
    Parkinson’s disease (PD) is a common neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra. Most investigations have focused on the cerebral regions such as the basal ganglia, thalamus, or the substantia nigra, but whether there is pathologic impairment within the cerebellum has rarely been assessed. Synapsin and neurofilament as the inner markers of neurons and synapses reflect the functional state by their distribution or expression. Significant morphologic changes at the cellular level have been demonstrated directly or indirectly in multiple neurodegenerative diseases. The purpose of this study was to determine whether the behavioral abnormalities that accompany PD are associated with the cerebellum using an in vivo 6- hydroxydopamine lesioned rat model. Forty-two rats were divided into three groups, the Parkinsonian group (N=22), sham group (N=10) and control group (N=10). The dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylaseimmunopositive cells. Immunohistochemical studies showed that the density of synapsin I in the granular layer of the cerebellum on both sides of the Parkinsonian -model was not statistically significantly different compared to the control and sham groups. However, expression of neurofilament H in the cortex within bilateral paramedian lobule (PML) and Crus 2 of the ansiform lobule (C2AL) in cerebellum posterior lobe of Parkinsonian rats was decreased compared with controls (P<0.05), especially in the loss of Purkinje cells and the presence of morphologic abnormalities in the cell nucleus. The study suggested that loss of neurons and synapses may take place in the cerebellar cortex of Parkinson’s disease, and might play an important role in the pathologic mechanism of PD.
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    Parkinson's disease: a short story of 200 years
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Cuenca, L.; Gil Martinez, A.L.; Cano Fernandez, L.; Sanchez Rodrigo, C.; Estrada, C.; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad
    After Alzheimer’s disease, Parkinson’s disease (PD) is the second most prevalent and incidental neurodegenerative disorder, affecting more than 2% of the population older than 65 years old. Since it was first described 200 years ago by Dr James Parkinson, great steps have been made in the understanding of the pathology. However, the cause(s) that initiates and perpetuates the neurodegenerative process is (are) still not clear. Thus, early diagnosis is not available, nor are there efficient therapies that can stop neurodegeneration. PD clinical features are defined by motor (like bradykinesia, resting tremor, gait impairment) and nonmotor symptoms (like constipation, apathy, fathigue, olfactory dysfunction, depression and cognitive decline) that get more severe as the disease advances. Neuropathological hallmarks comprise selective loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and Lewy bodies (LB) in different nuclei of the nervous system. Numerous studies have shown that these pathological features are aggravated by the confluence of other contributing factors, such as a genetic component, exposure to environmental toxins, mitochondrial dysfunction, increase of oxidative stress, calcium imbalance and chronic neuroinflammation, among others. Here, we provide a summary of the actual state of PD’s pathology, the most studied molecular mechanisms, classic and novel therapeutic strategies and diagnosis methods, especially highlighting recent advances in these 200 years