Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

Rizelio, Vanessa; Szawka, Raphael E.; Xavier, Léder Leal; Achaval, Matilde; Rigon, Paula; Saur, Lisiani; Matheussi, Francesca; Delattre, A; Anselmo-Franci, Janete Aparecida; Meneses, Murilo S.; Ferraz, Anete Curte

doi:10.1590/s0100-879x2009007500020

Cited by 23 publications

(4 citation statements)

References 38 publications

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“…The 6-OHDA-induced striatal lesion produces alterations in the locomotor activity, as evaluated by the open-field test [ 41 ]. We showed that untreated 6-OHDA-lesioned animals presented a significant reduction in the number of crossings/5 min, as related to the SO group, and such behavioral alteration was reversed after treatment with the higher VA dose.…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

Ximenes

Neves

Leal

et al. 2015

Journal of Neurodegenerative Diseases

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Parkinson's disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson's disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests). Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations), histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These results were observed not only in the CA1 and CA3 subfields of the hippocampus, but also in the temporal cortex. In conclusion, we showed that VA partly reversed the behavioral, neurochemical, histological, and immunohistochemical alterations observed in the untreated 6-OHDA-lesioned animals. These effects are probably related to the drug anti-inflammatory activity and strongly suggest that VA is a potential candidate to be included in translational studies for the treatment of neurodegenerative diseases as PD.

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Section: Discussionmentioning

confidence: 99%

Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

Ximenes

Neves

Leal

et al. 2015

Journal of Neurodegenerative Diseases

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“…Monoamines and metabolites were identified based on their peak retention times. Quantification was performed using the internal standard method based on the area under the peak (Rizelio et al, 2010;Szawka et al, 2010). All samples from each brain area were measured in the same analysis.…”

Section: Neurotransmitter Analysesmentioning

confidence: 99%

Intrinsic exercise capacity is related to differential monoaminergic activity in the rat forebrain

Rabelo

Almeida

Guimarães

et al. 2015

Brain Research Bulletin

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“…Neurochemical Assay DA and DOPAC levels in the striatum were determined by high performance liquid chromatography coupled with electrochemical detection (HPLC-ED) as previously described [19,22]. Briefly, the striatum was homogenized in 800 ll of a solution containing 0.2 M perchloric acid, 0.1 mM EDTA and 450 nM of 3,4-dihydroxybenzilamine (internal standard; Aldrich, Milwaukee, USA).…”

Section: -Ohda Lesionmentioning

confidence: 99%

Effect of Different Doses of Estrogen on the Nigrostriatal Dopaminergic System in Two 6-Hydroxydopamine-Induced Lesion Models of Parkinson’s Disease

et al. 2011

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Parkinson's disease results from a degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc) and it is more prevalent in men than in women. Estrogen has neuroprotective action of the nigrostriatal dopaminergic (NSDA) neurons. It was investigated whether differences in plasma 17β-estradiol (E2) levels alter the degree of neuroprotection in NSDA neurons. Ovariectomized rats, implanted with subcutaneous capsules containing 400, 800 or 1,600 μg of E2 or corn oil, were injected with 1 μg of 6-OHDA in the SNpc or the medial forebrain bundle (MFB). Striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and plasma E2 levels were measured. Only at 400 μg, E2 protected striatal DA against lesion of the MFB. In the SNpc, E2 failed to prevent DA depletion, but increased DOPAC/DA ratio in the striatum. In an NSDA moderate lesion, E2 has a neuroprotective action. In a severe lesion, E2 could stimulate DA activity in remaining neurons.

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Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

Cited by 23 publications

References 38 publications

Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

Intrinsic exercise capacity is related to differential monoaminergic activity in the rat forebrain

Effect of Different Doses of Estrogen on the Nigrostriatal Dopaminergic System in Two 6-Hydroxydopamine-Induced Lesion Models of Parkinson’s Disease

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