Hemiparkinsonian rats rotate toward the side with the weaker dopaminergic neurotransmission

Cunha, Cláudio Da; Wietzikoski, Evellyn Claudia; Ferro, Marcelo Machado; Martinez, Gláucia Regina; Vital, Maria A.B.F.; Hipólide, Débora Cristina; Tufik, Sérgio; Canteras, Newton S.

doi:10.1016/j.bbr.2008.01.012

Cited by 40 publications

(34 citation statements)

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“…Furthermore, in unilateral nigrostriatal-lesioned animals, administration of apomorphine (a non-selective dopamine agonist with a higher affinity for D2-like receptors) has been shown to induce turning behaviour contralateral to the lesioned side (Jerussi and Glick 1975;Cunha et al 2008). Fig.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

et al. 2014

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“…We investigated Locomotor Behavior Evaluation the pluripotency of the iPS cells reprogrammed from MEFs using EB formation and various differentiation Apomorphine-induced rotations were analyzed 2 days before and 1, 4, 8, and 12 weeks after transplantation, protocols (14). The iPS cells could be differentiated into cartilaginous, adipocyte-like (mesodermal), and hepatoto evaluate the effects of transplantation on symmetry of motor function (11,13). Mice were tested for rotation cyte-like (endodermal) cells, as confirmed by positive Safranin-O, Oil Red, and albumin staining, respectively in response to an intraperitoneal injection of 1 mg/kg apomorphine in PBS.…”

Section: Terminal Dutp Nick-end Labeling (Tunel) Assay In Experimentmentioning

confidence: 99%

Docosahexaenoic Acid Promotes Dopaminergic Differentiation in Induced Pluripotent Stem Cells and Inhibits Teratoma Formation in Rats with Parkinson-Like Pathology

et al. 2012

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic (DA) neurons in the midbrain. Induced pluripotent stem (iPS) cells have shown potential for differentiation and may become a resource of functional neurons for the treatment of PD. However, teratoma formation is a major concern for transplantation-based therapies. This study examined whether functional neurons could be efficiently generated from iPS cells using a five-step induction procedure combined with docosahexaenoic acid (DHA) treatment. We demonstrated that DHA, a ligand for the RXR/Nurr1 heterodimer, significantly activated expression of the Nurr1 gene and the Nurr1-related pathway in iPS cells. DHA treatment facilitated iPS differentiation into tyrosine hydroxylase (TH)-positive neurons in vitro and in vivo and functionally increased dopamine release in transplanted grafts in PD-like animals. Furthermore, DHA dramatically upregulated the endogenous expression levels of neuroprotective genes (Bcl-2, Bcl-xl, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor) and protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis in iPS-derived neuronal precursor cells. DHA-treated iPS cells significantly improved the behavior of 6-hydroxydopamine (6-OHDA)-treated PD-like rats compared to control or eicosapentaenoic acid-treated group. Importantly, the in vivo experiment suggests that DHA induces the differentiation of functional dopaminergic precursors and improves the abnormal behavior of 6-OHDAtreated PD-like rats by 4 months after transplantation. Furthermore, we found that DHA treatment in iPS cell-grafted rats significantly downregulated the mRNA expression of embryonic stem cell-specific genes (Oct-4 and c-Myc) in the graft and effectively blocked teratoma formation. Importantly, 3 Tesla-magnetic resonance imaging and ex vivo green fluorescence protein imaging revealed that no teratomas were present in transplanted grafts of DHA-treated iPS-derived DA neurons 4 months after implantation. Therefore, our data suggest that DHA plays a crucial role in iPS differentiation into functional DA neurons and that this approach could provide a novel therapeutic approach for PD treatment. INTRODUCTIONand psychiatric therapies (29). A recent study demonstrated that DHA protected against dendritic pathology Parkinson's disease (PD) is characterized by the proand behavioral deficits and increased the antiapoptotic gressive loss of a specific population of dopaminergic BCL2-associated agonist of cell death (BAD) phosphor-(DA) neurons in the brain, which leads to debilitating ylation associated with protection against Alzheimer's impairments in the control of movement and eventual disease (5). Furthermore, DHA has been used to prevent death (6,31,40). As PD results from the loss of DA neudecreases of DA and serotoninergic neurotransmitters in rons, the prospect of utilizing cell replacement therapies the frontal cortex of piglets fed linoleic acid-deficient for th...

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“…This rotation behavior occurs due to the imbalance of dopaminergic neurotransmission between injured and uninjured sides, so a larger lesion results in more rotations. This imbalance is caused by the overexpression of dopamine receptors in lesioned striatum, thus potentiating the apomorphine effect (Da Cunha et al, 2008, 2009.…”

Section: Methodsmentioning

confidence: 99%

“…and lesioned with 6-OHDA (Sigma-Aldrich Inc., St. Louis, MO, USA) (8 mg in 0.2% ascorbic acid 0.9% saline solution) on the left medial forebrain bundle following stereotaxic coordinates: anteroposteriorly -1.9 mm from the bregma; mediolaterally +1.9 mm from the midline; and dorsoventrally -7.9 mm from the skull (Paxinos, Watson, 1998;Da Cunha et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

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Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

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Schamne

Ferro

et al. 2015

Braz. J. Pharm. Sci.

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Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28 th day before surgery to the 7 th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD. Uniterms:Parkinson's disease/treatment/experimental study. H. perforatum/phytotherapy/neuroprotective effect. Turning behavior. 6-OHDA.A Doença de Parkinson é uma doença neurodegenerativa relacionada à idade, caracterizada pela morte lenta e progressiva de neurônios dopaminérgicos da substância negra pars compacta. O Hypericum perforatum (H. perforatum) é um fitoterápico utilizado como antidepressivo, apresentando propriedades antioxidantes, anti-inflamatórias e nootrópicas. Neste trabalho, avaliaram-se os efeitos do tratamento com H. perforatum no comportamento rotatório de ratos no modelo da doença de Parkinson induzido pela administração unilateral de 6-OHDA no feixe prosencefálico medial. Ratos Wistar machos foram tratados com H. perforatum (100, 200 ou 400 mg/kg, v.o.) por 35 dias (do 28º dia antes até o 7º dia após a lesão). As rotações ipsilaterais e contralaterais à lesão foram registradas no 7º, 14º e 21º dias após a cirurgia. As três doses de H. perforatum utilizadas reduziram o número de rotações contralaterais, indicando um possível efeito neuroprotetor da planta. Porém, o H. perforatum não impediu a redução na expressão da enzima tirosina hidroxilase no estriado lesionado, quantificada por Western blot. Propomos que o H. perforatum possa bloquear o aumento da expressão dos receptores dopaminérgicos no estriado lesionado com 6-OHDA. Entretanto, estudos adicionais são necessários para identificar o mecanismo exato pelo qual o H. perforatum reduziu o número de rotações contralaterais. Os resultados do presente estudo sugerem o H. perforatum como um potencial agente terapêutico para a doença de Parkinson.Unitermos: Doença de Parkinson/tratamento/estudo ...

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Hemiparkinsonian rats rotate toward the side with the weaker dopaminergic neurotransmission

Cited by 40 publications

References 44 publications

Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

Docosahexaenoic Acid Promotes Dopaminergic Differentiation in Induced Pluripotent Stem Cells and Inhibits Teratoma Formation in Rats with Parkinson-Like Pathology

Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

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