Giordano Gubert Viola

Federal University of Santa Catarina, Nossa Senhora do Destêrro, Santa Catarina, Brazil

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Publications (16)44.23 Total impact

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    ABSTRACT: Deposition of amyloid-β (Aβ) peptides into specific encephalic structures has been pointed as an important event related to Alzheimer's disease pathogenesis and associated with activation of glial cells, neuroinflammation, oxidative responses, and cognitive deficits. Aβ-induced pro-oxidative damage may regulate the activity of glutamate transporters, leading to reduced glutamate uptake and, as a consequence, excitotoxic events. Herein, we evaluated the effects of the pretreatment of atorvastatin, a HMG-CoA reductase inhibitor, on behavioral and biochemical alterations induced by a single intracerebroventricular (i.c.v.) injection of aggregated Aβ1-40 in mice. Atorvastatin (10 mg/kg/day, p.o.) was administered through seven consecutive days before Aβ1-40 administration. Aβ1-40 caused significant cognitive impairment in the object-place recognition task (2 weeks after the i.c.v. injection) and this phenomenon was abolished by atorvastatin pretreatment. Ex vivo evaluation of glutamate uptake into hippocampal and cerebral cortices slices showed atorvastatin, and Aβ1-40 decreased hippocampal and cortical Na(+)-dependent glutamate uptake. However, Aβ1-40 increased Na(+)-independent glutamate uptake and it was prevented by atorvastatin in prefrontal cortex slices. Moreover, Aβ1-40 treatment significantly increased the cerebrocortical activities of glutathione reductase and glutathione peroxidase and these events were blunted by atorvastatin pretreatment. Reduced or oxidized glutathione levels were not altered by Aβ1-40 and/or atorvastatin treatment. These results extend the notion of the protective action of atorvastatin against neuronal toxicity induced by Aβ1-40 demonstrating that a pretreatment with atorvastatin prevents the spatial learning and memory deficits induced by Aβ in rodents and promotes changes in glutamatergic and antioxidant systems mainly in prefrontal cortex.
    Neurotoxicity Research 04/2015; 28(1). DOI:10.1007/s12640-015-9527-y · 3.15 Impact Factor
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    ABSTRACT: Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby inhibiting cell synthesis of cholesterol and isoprenoids. Moreover, several studies have been evaluating pleiotropic effects of statins, mainly because they present neuroprotective effects in various pathological conditions. However, knowledge about behavioral effects of statins per se is relatively scarce. Considering these facts, we aimed to analyze behavioral responses of atorvastatin or simvastatin-treated mice in the open field test, elevated plus maze and object location test. Atorvastatin treatment for 7 consecutive days at 1 mg/Kg or 10 mg/Kg (v.o.) or simvastatin 10 mg/Kg or 20 mg/Kg enhanced cognitive performance in object location test when compared to control group (saline-treated mice). Simvastatin effects on mice performance in the object location test was abolished by post-training infusion of the beta-adrenoceptor antagonist propranolol. Atorvastatin and simvastatin did not change the behavioral response in open field and elevated plus-maze (EPM) tests in any of used doses. These data demonstrate the positive effects of both statins in cognitive processes in mice, without any alteration in locomotor parameters in the open field test or anxiolytic-like behavior in EPM. In conclusion, we demonstrate that atorvastatin and simvastatin per se improves the cognitive performance in a rodent model of spatial memory and this effect is related to beta-adrenergic receptors modulation. Copyright © 2015. Published by Elsevier Inc.
    Physiology & Behavior 02/2015; 143. DOI:10.1016/j.physbeh.2015.02.024 · 3.03 Impact Factor
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    Giordano Gubert Viola, Cássio Morais Loss
    Brain Structure and Function 05/2013; 219(4). DOI:10.1007/s00429-013-0563-1 · 4.57 Impact Factor
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    ABSTRACT: Affective disorders and memory impairments precede the classical motor symptoms seen in Parkinson's disease (PD) and the currently approved antiparkinsonian agents do not alleviate the non-motor symptoms as well as the underlying dopaminergic neuron degeneration. On the other hand, there is increasing evidence that inflammation plays a key role in the pathophysiology of PD and that the anti-inflammatory actions of statins are related to their neuroprotective properties against different insults in the CNS. The present data indicates that the oral treatment with atorvastatin (10mg/kg/day), once a day during 7 consecutive days, was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1mg/nostril). Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover, atorvastatin was found to protect against the long-lasting motor deficits evaluated in activity chambers and the loss of dopaminergic neurons in the substantia nigra pars compacta observed at 21 days after i.n. MPTP administration. At this time, despite the absence of spatial memory deficits in the water maze and in concentrations of the cytokines TNF-α, IL-1β and IL-10 in striatum and hippocampus following i.n. MPTP administration, atorvastatin treatment resulted in a significant increase in the striatal and hippocampal levels of nerve growth factor (NGF). These findings reinforce and extend the notion of the neuroprotective potential of atorvastatin and suggest that it may represent a new therapeutic tool for the management of motor and non-motor symptoms of PD.
    Brain research 03/2013; 1513. DOI:10.1016/j.brainres.2013.03.029 · 2.83 Impact Factor
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    ABSTRACT: Vascular disease is a major cause of morbidity and mortality among transplanted recipients and cyclosporine (CsA) treatment has been consistently implicated in this event. In this study we assessed total blood homocysteine levels (tHcy), ecto-nucleotidase activities and adenine nucleotide/nucleoside levels searching for parameters related to the mechanisms of vascular damage induced by chronic CsA treatment in non-transplanted rats. Thirty male Wistar rats were divided in three groups: control group treated with corn oil, CsA 5mg/kg and CsA 15 mg/kg, administered by daily gastric gavage during 8 weeks. CsA 15 mg/kg treatment increased blood levels of tHcy. Both CsA treatments (5mg/kg and 15 mg/kg) decreased adenine nucleotides hydrolysis by ecto-nucleotidases in serum, which negatively correlated with tHcy levels (r: -0.74, r: -0.63 and r: -0.63, p<0.004, for ATP, ADP and AMP, respectively). CsA 15mg/kg induced a statistically significant increase in ADP and decrease in adenosine (ADO) plasma levels compared to control group. THcy levels were positively correlated with plasma ADP levels and negatively correlated with ADO levels (r: 0.84, p<0.0001 and r: -0.68, p<0.0001, respectively). Rats under CsA 15 mg/kg treatment presented cell injury and inflammatory responses in the endothelium and intima layer of the aorta artery. In conclusion, blood ecto-nucleotidases activity, tHcy, and ADP and ADO levels may be implicated in vascular injury induced by CsA treatment.
    Chemico-biological interactions 10/2010; 188(1):15-20. DOI:10.1016/j.cbi.2010.06.011 · 2.98 Impact Factor
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    ABSTRACT: Diphenyl diselenide (PhSe)(2) is a selenium organic compound that has been described to inhibit glutamate binding at synaptic membranes and uptake into cortical slices, but there are no studies about its effects on glutamate transporters and related synaptic proteins. Hippocampal slices from rats treated acutely with (PhSe)(2) (1, 10, and 100 mg/kg, oral route) were evaluated on glutamate uptake, redox state, the immunocontent of glial (glutamate/aspartate transporter [GLAST] and glutamate transporter type I [GLT1]), neuronal (excitatory amino acid carrier 1 [EAAC1]), and vesicular (vesicular glutamate transporter 1 [VGLUT1]) glutamate transporters. Besides, cell viability was evaluated by glial fibrillar acid protein (GFAP) and synaptosomal-associated protein 25 (SNAP-25) immunocontent and 4', 6-diamidino-2-phenylindole (DAPI) and Fluoro Jade C staining. Hippocampal slices from rats treated with (PhSe)(2) exhibited a nondose-dependent inhibition of glutamate uptake (53, 38, and 45%, respectively). All doses increased EAAC1, decreased SNAP-25, did not modify GLT1 immunocontent, and there was no evidence of oxidative stress. (PhSe)(2) (100 mg/kg) increased 32% GLAST, decreased 34% VGLUT1, and 21% GFAP immunocontent. Besides, (PhSe)(2) (100 mg/kg) decreased by 25% GFAP-stained astrocytes and 27% DAPI-stained cells in the CA1 subfield. Our results suggest that the increase of EAAC1 and GLAST immunocontent by (PhSe)(2) might be a compensatory mechanism by surviving cells in order to reduce extracellular glutamate levels, avoiding possible neurotoxic effects. The impairment of glutamate uptake by the highest dose of (PhSe)(2) seems to be related to a decrease on VGLUT1, SNAP-25, and damage to astrocytes. Since there were no signs of oxidative stress, our findings revealed that depending on the dose, acute administration of (PhSe)(2) causes modifications in important synaptic-related proteins and damage to the astrocytes, and these events must be taken into account in its pharmacological properties.
    Toxicological Sciences 11/2009; 113(2):434-43. DOI:10.1093/toxsci/kfp282 · 4.48 Impact Factor
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    ABSTRACT: Environmental enrichment (EE) is an experimental model for studying neuroplasticity. EE is used to investigate behavioral modifications associated with gene-environmental interaction. The object recognition task (ORT) evaluates animals' ability to learn about their environment, which depends on their innate instinct. By using young CF1 mice, the present study evaluated the effect of 8 weeks of EE on the ORT. Our results indicate that EE decreased the time the animals spent exploring familiar and unfamiliar objects and total time spent exploring both objects, without affecting the capacity of discrimination of objects. These findings indicate a more propitious behavior for species survival in animals subjected to EE, including rapid exploration and learning about the environment.
    Physiology & Behavior 10/2009; 99(1):17-21. DOI:10.1016/j.physbeh.2009.10.003 · 3.03 Impact Factor
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    ABSTRACT: Environmental enrichment is known to induce plastic changes in the brain, including morphological changes in hippocampal neurons, with increases in synaptic and spine densities. In recent years, the evidence for a role of astrocytes in regulating synaptic transmission and plasticity has increased, and it is likely that morphological and functional changes in astrocytes play an important role in brain plasticity. Our study was designed to evaluate changes in astrocytes induced by environmental enrichment in the CA1 region of the hippocampus, focusing on astrocytic density and on morphological changes in astrocytic processes. After 8 weeks of environmental enrichment starting at weaning, male CF-1 mice presented no significant changes in astrocyte number or in the density of glial fibrillary acidic protein (GFAP) immunoreactivity in the stratum radiatum. However, they did present changes in astrocytic morphology in the same region, as expressed by a significant increase in the ramification of astrocytic processes measured by the Sholl concentric circles method, as well as by an increase in the number and length of primary processes extending in a parallel orientation to CA1 nerve fibers. This led astrocytes to acquire a more stellate morphology, a fact which could be related to the increase in hippocampal synaptic density observed in previous studies. These findings corroborate the idea that structural changes in astrocytic networks are an integral part of plasticity processes occurring in the brain.
    Brain research 05/2009; 1274:47-54. DOI:10.1016/j.brainres.2009.04.007 · 2.83 Impact Factor
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    ABSTRACT: Pentylenetetrazol (PTZ) is commonly used as a convulsant drug. The enhanced seizure susceptibility induced by kindling is probably attributable to plastic changes in the synaptic efficacy. Adenosine and guanosine act both as important neuromodulators and neuroprotectors with mostly inhibitory effects on neuronal activity. Adenosine and guanosine can be released per se or generated from released nucleotides (ATP, ADP, AMP, GTP, GDP, and GMP) that are metabolized and rapidly converted to adenosine and guanosine. The aim of this study was to evaluate nucleotide hydrolysis by ecto- and soluble nucleotidases (hippocampal slices and CSF, respectively) after PTZ-kindling (stages 3, 4, or 5 seizures) or saline treatment in rats. Additionally, the levels of purines in rat cerebrospinal fluid (CSF), as well as ecto-NTPDases (1, 2, 3, 5, 6 and 8) and ecto- 5'-nucleotidase expression were determined. Ecto-enzyme assays demonstrated that ATP, AMP, GDP, and GMP hydrolysis enhanced when compared with controls. In addition, there was an increase of ADP, GDP, and GMP hydrolysis by soluble nucleotidases in PTZ-kindling rats compared to control group. The HPLC analysis showed a marked increase in PTZ-kindled CSF concentrations of GTP, ADP, and uric acid, but GDP, AMP, and hypoxanthine concentrations were decreased. Such alterations indicate that the modulatory role of purines in CNS could be affected by PTZ-kindling. However, the physiological significance of these findings remains to be elucidated.
    Epilepsy Research 08/2007; 75(2-3):104-11. DOI:10.1016/j.eplepsyres.2007.04.006 · 2.19 Impact Factor
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    ABSTRACT: The medial amygdala (MeA) is a sexually dimorphic area that modulates neuroendocrine and behavioral activities and where gonadal hormones play an important role in neuron-glial and synaptic plasticity. Immunohistochemistry was used to identify the astrocytic marker glial fibrillary acidic protein (GFAP) in the different MeA subnuclei--anterodorsal (MeAD), posterodorsal (MePD) and posteroventral (MePV)--of intact female rats in the different phases of the estrous cycle and in ovariectomized females treated with hormonal substitutive therapy. Data semi-quantified by optical densitometry showed that, in the proestrus phase, the GFAP immunoreactivity (GFAP-ir) was higher when compared to the other phases of the estrous cycle (P < 0.02). GFAP-ir was also higher in the MePD than in the MeAD or in the MePV (P < 0. 02). In ovariectomized females, injections of estradiol alone or estradiol plus progesterone increased GFAP-ir in the MePD and in the MePV (P < 0.001), but not in the MeAD (P > 0.3), when compared to control data. These findings suggest that astrocytic GFAP in the MeA subnuclei can be affected either by physiological levels or by hormonal manipulation of the ovarian steroids, which may contribute to the plasticity of local and integrated functional activities of these brain areas in female rats.
    Brain Research 09/2006; 1108(1):117-26. DOI:10.1016/j.brainres.2006.06.014 · 2.83 Impact Factor
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    ABSTRACT: Parkinson's disease is a progressive dyskinetic disorder caused by degeneration of mesencephalic dopaminergic neurons in the substantia nigra pars compacta (SNpc) and, to a lesser extent, in the ventral tegmental area (VTA). Tyrosine hydroxylase (TH) is a rate-limiting enzyme for dopamine synthesis, therefore immunohistochemistry for TH can be used as an important marker of dopaminergic cell loss in these regions. Traditionally, immunohistochemical experiments are analyzed qualitatively by optical microscopic observation or more rarely semi-quantitatively evaluated by densitometry. A common problem with such papers is the lack of a clear explanation of the algorithms and macros employed in the semi-quantitative approaches. In this paper, we describe, in detail, an easy, fast and precise protocol for the analysis of TH immunoreactivity in SNpc and VTA using one of the most popular image analysis software packages (Image Pro-Plus). We believe that this protocol will facilitate the evaluation of mesencephalic TH immunoreactivity in various available animal models of Parkinson's disease.
    Brain Research Protocols 01/2006; 16(1-3):58-64. DOI:10.1016/j.brainresprot.2005.10.002 · 1.82 Impact Factor
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    ABSTRACT: We describe the behavior of the snail Megalobulimus abbreviatus upon receiving thermal stimuli and the effects of pretreatment with morphine and naloxone on behavior after a thermal stimulus, in order to establish a useful model for nociceptive experiments. Snails submitted to non-functional (22 degrees C) and non-thermal hot-plate stress (30 degrees C) only displayed exploratory behavior. However, the animals submitted to a thermal stimulus (50 degrees C) displayed biphasic avoidance behavior. Latency was measured from the time the animal was placed on the hot plate to the time when the animal lifted the head-foot complex 1 cm from the substrate, indicating aversive thermal behavior. Other animals were pretreated with morphine (5, 10, 20 mg/kg) or naloxone (2.5, 5.0, 7.5 mg/kg) 15 min prior to receiving a thermal stimulus (50 degrees C; N = 9 in each group). The results (means +/- SD) showed an extremely significant difference in response latency between the group treated with 20 mg/kg morphine (63.18 +/- 14.47 s) and the other experimental groups (P < 0.001). With 2.5 mg/kg (16.26 +/- 3.19 s), 5.0 mg/kg (11.53 +/- 1.64 s) and 7.5 mg/kg naloxone (7.38 +/- 1.6 s), there was a significant, not dose-dependent decrease in latency compared to the control (33.44 +/- 8.53 s) and saline groups (29.1 +/- 9.91 s). No statistically significant difference was found between the naloxone-treated groups. With naloxone plus morphine, there was a significant decrease in latency when compared to all other groups (minimum 64% in the saline group and maximum 83.2% decrease in the morphine group). These results provide evidence of the involvement of endogenous opioid peptides in the control of thermal withdrawal behavior in this snail, and reveal a stereotyped and reproducible avoidance behavior for this snail species, which could be studied in other pharmacological and neurophysiological studies.
    Brazilian Journal of Medical and Biological Research 02/2005; 38(1):73-80. DOI:10.1590/S0100-879X2005000100012 · 1.03 Impact Factor
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    ABSTRACT: Using immunohistochemistry and optical densitometry, somatostatin (SOM), calcitonin gene-related peptide (CGRP), and γ-aminobutyric acid (GABA) were investigated in the lumbosacral spinal cord of the frog Rana catesbeiana after sciatic nerve transection. In control animals, the densest network of the SOM-, CGRP- and GABA-like immunoreactive fibers was located in the dorsal part of the lateral funiculus. SOM and GABA-like fibers were found in the dorsal terminal field and in the mediolateral band. The latter region showed CGRP and SOM-like immunoreactive cell bodies. SOM- and GABA-like immunoreactive neurons also occurred around the cavity of the central canal, and other GABA-like fibers were found in the ventral terminal field. While the ventral horn showed scarce somatostatin-like fibers, the putative motoneurons were immunoreactive for the two peptides investigated and GABA, but only a few SOM- and GABA-like fibers occurred in the ventral funiculus. After axotomy, GABA-like immunoreactivity decreased in the dorsal part of the lateral funiculus on the same side of the lesion. The other regions remained labeled. These changes were observed at 3 days following axonal injury and persisted at 5, 8 and 15 days. There was no significant difference in the pattern of CGRP- and SOM- immunoreactivity between the axotomized and the control sides. These results are discussed in relation to the effects of the peripheral axotomy on GABA, SOM, and CGRP expression in vertebrates, emphasizing the use of frogs as a model to study the effects of peripheral nerve injury.
    Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 05/2004; 138(1):19-28. DOI:10.1016/j.cbpc.2004.01.004 · 1.90 Impact Factor
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    ABSTRACT: Unilateral neonatal hypoxia-ischemia causes important damage to the hippocampus of the hemisphere ipsilateral to carotid artery occlusion; two forms of neonatal handling, tactile stimulation and maternal separation for a short period, have been shown to produce functional/behavioral protection in distinct models of CNS challenge. In this paper we investigated whether neonatal handling could alter the hippocampal damage caused by neonatal hypoxia-ischemia (HI) in the Wistar rat. Pups at postnatal day 7, P7, received HI (8% O(2)-92% N(2)) for 90 min and were submitted to neonatal handling, tactile stimulation of maternal separation daily, from P8 to P21, for 10 min. On adulthood, hippocampal volume was analyzed by stereological techniques, along with measures of cortical thickness and hemispheric area at the level -3.30 mm from bregma. HI caused a reduction of volume of whole hippocampus, of Amon's horn and of dentate gyrus, with no effect on cortical and hemispheric measures; neonatal handling prevented such effect. This is the first report showing that both tactile stimulation and neonatal handling exert a morphological neuroprotective action for HI-induced damage to the hippocampus.
    Brain Research 04/2004; 1002(1-2):94-9. DOI:10.1016/j.brainres.2003.12.020 · 2.83 Impact Factor
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    ABSTRACT: The immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and in the ventral tegmental area (VTA) after intranigral infusion of 6-hydroxydopamine (6-OHDA, 6 microg/side) was analyzed in ovariectomized adult female Wistar rats. Estrogen replacement for 52 days (400-microg 17-beta-estradiol capsules) did not prevent the loss of TH-immunoreactive cells induced by 6-OHDA in the SNpc. This result indicates that the neuroprotective effect of dopaminergic mesencephalic cells is not observed with long-term estrogen replacement.
    Brain Research 11/2003; 986(1-2):200-5. DOI:10.1016/S0006-8993(03)03198-6 · 2.83 Impact Factor
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    ABSTRACT: Using immunohistochemistry and optical densitometry, substance P (SP) was investigated in the lumbar spinal cord of the frog Rana catesbeiana after sciatic nerve transection. In control animals, there was a high density of SP fibers in the Lissauer's tract and in the mediolateral band of the dorsal gray matter. Other SP immunoreactive fibers were observed in the dorsal part of the lateral funiculus and in the ventral horn. No SP label was found in any cell bodies. After axotomy, SP immunoreactive fibers decreased in the Lissauer's tract on the same side of the lesion. The other regions remained labeled. The changes were observed at 3 days following axonal injury and persisted at 5, 8 and 15 days. At 20 days, there was no significant difference between the axotomized side and the control one, thus indicating a recovery of the SP expression. These results indicate that the frog may be used as a model to study the effects of peripheral axotomy, contributing to elucidate the SP actions in the pain neuropath.
    Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 05/2002; 131(4):807-14. DOI:10.1016/S1096-4959(02)00041-6 · 1.90 Impact Factor

Publication Stats

270 Citations
44.23 Total Impact Points

Institutions

  • 2013
    • Federal University of Santa Catarina
      • Departamento de Bioquímica
      Nossa Senhora do Destêrro, Santa Catarina, Brazil
  • 2002–2010
    • Universidade Federal do Rio Grande do Sul
      • • Departamento de Bioquímica
      • • Departamento de Ciências Morfológicas
      • • Institute of Basic Sciences and Health
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil