RESUMO
Carvacrol is a monoterpene that has been linked to neuroprotection in several animal models of neurodegeneration, including ischemia, epilepsy and traumatic neuronal injury. In this study, we investigated the effects of carvacrol (i.p.) upon the neurodegeneration induced by 6-hydroxy-dopamine unilateral intrastriatal injections in mice. We have also used the cylinder test to assess the behavioral effects of carvacrol in that model of Parkinson's disease, and immunoblots to evaluate the levels of caspase-3 and TRPM7, one of major targets of carvacrol. Behavioral testing revealed that carvacrol largely reduced the asymmetrical use of the forelimbs induced by unilateral 6-hydroxy-dopamine. Carvacrol dramatically reduced the loss of tyrosine hydroxylase immunostaining both in the substantia nigra and in the striatum that are typical of the model. Immunoblots for tyrosine hydroxylase confirmed this effect. Caspase-3 levels were very high after toxin injections, but carvacrol appeared to reduce them to control levels. Finally, TRPM7, observed by immunoblots, increased after 6-hydroxy-dopamine, suggesting the involvement of this cation channel in the ensuing neurodegenerative process. The present data suggest that carvacrol promotes a marked neuroprotection in the 6-hydroxy-dopamine model of Parkinson's disease, possibly by its non-specific blocking effect upon TRPM7 channels.
Assuntos
Monoterpenos/farmacologia , Neurônios/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Substância Negra/efeitos dos fármacos , Animais , Cimenos , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismoRESUMO
The loss of nigral dopaminergic neurons typical in Parkinson's disease (PD) is responsible for hyperexcitability of medium spiny neurons resulting in abnormal corticostriatal glutamatergic synaptic drive. Considering the neuroprotective effect of exercise, the changes promoted by exercise on AMPA-type glutamate receptors (AMPARs), and the role of activity-regulated cytoskeleton-associated protein (Arc) in the AMPARs trafficking, we studied the impact of short and long-term treadmill exercise during evolution of the unilateral 6-hydroxy-dopamine (6-OHDA) animal model of PD. Wistar rats were divided into sedentary and exercised groups, with and without lesion by 6-OHDA and followed up to 4 months. The exercised groups were subjected to a moderate treadmill exercise 3×/week. We measured the proteins tyrosine hydroxylase (TH), Arc, GluA1, and GluA2/3 in the striatum, substantia nigra, and motor cortex. Our results showed a higher reduction of TH expression in all sedentary groups when compared to all exercised groups in striatum and substantia nigra. In general, larger changes occurred in the striatum in the first and third months after training. After 1 month of exercise, there was significant increase of GluA2/3 with concomitant reduction of GluA1 and Arc. As a balanced system, these changes were reversed in the third month, showing an increase of Arc and GluA1 and decrease of GluA2/3. Similar results for GluAs and Arc were observed in the motor cortex of the exercised animals. These modifications may be relevant for corticostriatal circuits in PD, since the exercise-dependent plasticity can modulate GluAs expression and maybe neuronal excitability.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Atividade Motora , Proteínas do Tecido Nervoso/metabolismo , Doença de Parkinson/metabolismo , Condicionamento Físico Animal , Receptores de AMPA/metabolismo , Animais , Corpo Estriado/metabolismo , Proteínas do Citoesqueleto/genética , Masculino , Córtex Motor/metabolismo , Proteínas do Tecido Nervoso/genética , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/fisiopatologia , Ratos , Ratos Wistar , Receptores de AMPA/genética , Substância Negra/metabolismoRESUMO
Physical exercise is known to produce beneficial effects to the nervous system. In most cases, brain-derived neurotrophic factor (BDNF) is involved in such effects. However, little is known on the role of BDNF in exercise-related effects on Parkinson's disease (PD). The aim of this study was to investigate the effects of intermittent treadmill exercise-induced behavioral and histological/neurochemical changes in a rat model of unilateral PD induced by striatal injection of 6-hydroxydopamine (6-OHDA), and the role of BDNF in the exercise effects. Adult male Wistar rats were divided into two main groups: (1) injection of K252a (a blocker of BDNF receptors), and (2) without BDNF receptor blockade. These groups were then subdivided into four groups: control (CLT), sedentary (SED, non-exercised with induction of PD), exercised 3×/week during four weeks before and four weeks after the induction of PD (EXB+EXA), and exercised 3×/week during four weeks after the induction of PD (EXA). One month after 6-OHDA injections, the animals were subjected to rotational behavioral test induced by apomorphine and the brains were collected for immunohistochemistry and immunoblotting assays, in which we measured BDNF and tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and the striatum (caudate-putamen, CPu). Our results showed a significant reduction of rotational asymmetry induced by apomorphine in the exercised parkinsonian rats. BDNF decreased in the SNc of the SED group, and exercise was able to revert that effect. Exercised groups exhibited reduced damage to the dopaminergic system, detected as a decreased drop of TH levels in SNc and CPu. On the other hand, BDNF blockade was capable of substantially reducing TH expression postlesion, implying enhanced dopaminergic cell loss. Our data revealed that physical exercise is capable of reducing the damage induced by 6-OHDA, and that BDNF receptors are involved in that effect.
Assuntos
Terapia por Exercício/métodos , Doença de Parkinson/reabilitação , Receptor trkB/metabolismo , Análise de Variância , Animais , Apomorfina , Carbazóis/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Teste de Esforço , Regulação da Expressão Gênica/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Masculino , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Putamen/efeitos dos fármacos , Putamen/fisiologia , Ratos , Ratos Wistar , Comportamento Estereotipado/efeitos dos fármacos , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Redox processes associated with controlled generation of reactive oxygen species (ROS) by NADPH oxidase (Nox) add an essential level of regulation to signaling pathways underlying physiological processes. We evaluated the ROS generation in the main visual relays of the mammalian brain, namely the superior colliculus (SC) and the dorsal lateral geniculate nucleus (DLG), after ocular enucleation in adult rats. Dihydroethidium (DHE) oxidation revealed increased ROS generation in SC and DLG between 1 and 30 days postlesion. ROS generation was decreased by the Nox inhibitors diphenyleneiodonium chloride (DPI) and apocynin. Real-time PCR results revealed that Nox 2 was upregulated in both retinorecipient structures after deafferentation, whereas Nox 1 and Nox 4 were upregulated only in the SC. To evaluate the role of ROS in structural remodeling after the lesions, apocynin was given to enucleated rats and immunohistochemistry was conducted for markers of neuronal remodeling into SC and DLG. Immunohistochemical data showed that ocular enucleation produces an increase of neurofilament and microtubule-associated protein-2 immunostaining in both SC and DLG, which was markedly attenuated by apocynin treatment. Taken together, the findings of the present study suggest a novel role for Nox-induced ROS signaling in mediating neuronal remodeling in visual areas after ocular enucleation.
Assuntos
Corpos Geniculados/metabolismo , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Colículos Superiores/metabolismo , Vias Visuais/metabolismo , Animais , Biomarcadores/metabolismo , Etídio/análogos & derivados , Etídio/metabolismo , Enucleação Ocular , Corpos Geniculados/citologia , Immunoblotting , Imuno-Histoquímica , Isoenzimas/antagonistas & inibidores , Isoenzimas/fisiologia , Masculino , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/fisiologia , Plasticidade Neuronal , Neurônios/ultraestrutura , Oxirredução , Reação em Cadeia da Polimerase , Ratos , Ratos Wistar , Colículos Superiores/citologia , Vias Visuais/citologiaRESUMO
How the considerable diversity of neural crest (NC)-derived cell types arises in the vertebrate embryo has long been a key question in developmental biology. The pluripotency and plasticity of differentiation of the NC cell population has been fully documented and it is well-established that environmental cues play an important role in patterning the NC derivatives throughout the body. Over the past decade, in vivo and in vitro cellular approaches have unravelled the differentiation potentialities of single NC cells and led to the discovery of NC stem cells. Although it is clear that the final fate of individual cells is in agreement with their final position within the embryo, it has to be stressed that the NC cells that reach target sites are pluripotent and further restrictions occur only late in development. It is therefore a heterogenous collection of cells that is submitted to local environmental signals in the various NC-derived structures. Several factors were thus identified which favor the development of subsets of NC-derived cells in vitro. Moreover, the strategy of gene targeting in mouse has led at identifying new molecules able to control one or several aspects of NC cell differentiation in vivo. Endothelin peptides (and endothelin receptors) are among those. The conjunction of recent data obtained in mouse and avian embryos and reviewed here contributes to a better understanding of the action of the endothelin signaling pathway in the emergence and stability of NC-derived cell phenotypes.
Assuntos
Diferenciação Celular/fisiologia , Endotelina-3/fisiologia , Crista Neural/embriologia , Plasticidade Neuronal/fisiologia , Células-Tronco/fisiologia , Animais , Diferenciação Celular/genética , Embrião de Galinha , Variação Genética , Camundongos , Crista Neural/fisiologia , Plasticidade Neuronal/genéticaRESUMO
El propósito de este estudio fue revisar los resultados quirúrgicos inmediatos en la cirugía de la úlcera gástrica durante 12 años en nuestro Hospital. Se hace notar el alto porcentaje de úlceras subcardiales, y el tipo de cirugía empleada. Se destaca, los buenos resultados, con mortalidad de 0,68%, a pesar de incluir la cirugía de urgencia