Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

Ferro, Marcelo Machado; Bellissimo, Maria Ines; Anselmo-Franci, Janete Aparecida; Angellucci, Miriam Elizabeth Mendes; Canteras, Newton S.; Cunha, Cláudio Da

doi:10.1016/j.jneumeth.2005.04.005

Cited by 188 publications

(118 citation statements)

References 70 publications

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“…Three weeks after gavage procedure, MPTP and MPTP+DHA animals were anesthetized with 400 mg/kg chloral hydrate (K91627425, Merck KGaA, Darmstadt, Germany) intraperitoneally. MPTP (M-0896, Sigma-Aldrich, St. Louis, Mo,USA ) (100 g/1 l saline) was infused bilaterally into the medial forebrain bundle using a Hamilton microsyringe at a rate of 0.33 l/min [11], according to the following coordinates adapted from the Pellegrino's atlas [12]: anteroposterior (AP) 2.2 mm from the bregma, mediolateral (ML) ±1.5 mm from midline and dorsoventral (DV) 8.0 mm from the skull. After surgery, animals were allowed to recover from anesthesia in a temperature controlled chamber and then placed in individual cages.…”

Section: Animalsmentioning

confidence: 99%

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Tanrıöver

Seval-Celik²,

Özsoy³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:Parkinson's disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases.

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Section: Animalsmentioning

confidence: 99%

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Tanrıöver

Seval-Celik²,

Özsoy³

et al. 2010

Folia Histochem Cytobiol.

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“…In particular, loss of dopamine cells in Parkinson's disease and its animal models leads to motor symptoms of rigidity, akinesia, and tremor (Schwarting & Huston, 1996;Kirik et al, 1998;Ferro et al, 2005), and the striatum is the main locus of dopamine's action, containing the highest density of dopamine receptors in the vertebrate brain (Dawson et al, 1986;Richtand et al, 1995;Hurd et al, 2001). Moreover, an intact dopamine system also seems to be critical for many forms of learning (Whishaw & Dunnett, 1985;Ferro et al, 2005), consistent with reported correlations between dopamine cell firing and the prediction error required by reinforcement learning theories (Redgrave & Gurney, 2006;Schultz, 2007). An intact striatum is similarly required for successful acquisition of many instrumental conditioning tasks (Yin & Knowlton, 2006).…”

Section: Introductionmentioning

confidence: 99%

Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit

2009

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The striatum, principal input structure of the basal ganglia, is crucial to both motor control and learning. It receives convergent input from all over neocortex, hippocampal formation, amygdala and thalamus, and is the primary recipient of dopamine in the brain. Within the striatum is a GABAergic microcircuit that acts upon these inputs, formed by the dominant medium-spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs). There has been little progress in understanding the computations it performs, hampered by the non-laminar structure that prevents identification of a repeating canonical microcircuit. We here begin the identification of potential dynamically-defined computational elements within the striatum. We construct a new three-dimensional model of the striatal microcircuit's connectivity, and instantiate this with our dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs is introduced and tuned to experimental data. We introduce a novel multiple spiketrain analysis method, and apply this to the outputs of the model to find groups of synchronised neurons at multiple time-scales. We find that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appear, consistent with experimental observations, and that the number of assemblies and the time-scale of synchronisation is strongly dependent on the simulated concentration of dopamine. We also show that feed-forward inhibition from the FSIs counter-intuitively increases the firing rate of the MSNs. Such small cell assemblies forming spontaneously only in the absence of dopamine may contribute to motor control problems seen in humans and animals following loss of dopamine cells.

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“…Cognitive deficits have been reported in rat models (4,6,7,20,21) and in the early stages of Parkinson's disease, even before the onset of motor symptoms (22). Since MPTP-and 6-OHDA-lesioned rats model the early and advanced phases of Parkinson's disease, respectively, the present results encourage future studies to test whether the observed neuroprotective effect of K/X would delay neurodegeneration in both phases of this disease.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

Ferro¹,

Angelucci²,

Anselmo-Franci³

et al. 2007

Braz J Med Biol Res

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There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side) or 6-OHDA (10 µg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67%) or severe (~91%) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP-and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

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Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

Cited by 188 publications

References 70 publications

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit

Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

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