RESUMO
Adult neurogenesis has been reported in all major vertebrate taxa. However, neurogenic rates and the number of neurogenic foci vary greatly, and are higher in ancestral taxa. Our study aimed to evaluate the distribution of doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in telencephalic areas of the adult tropical lizard Tropidurus hispidus. We describe evidence for four main neurogenic foci, which coincide anatomically with the ventricular sulci described by the literature. Based on neuronal morphology, we infer four migratory patterns/pathways. In the cortex, patterns of GFAP and DCX staining support radial migrations from ventricular zones into cortical areas and dorsoventricular ridge. Cells radiating from the sulcus septomedialis (SM) seemed to migrate to the medial cortex and dorsal cortex. From the sulcus lateralis (SL), they seemed to be bound for the lateral cortex, central amygdala and nucleus sphericus. We describe a DCX-positive stream originating in the caudal sulcus ventralis and seemingly bound for the olfactory bulb, resembling a rostral migratory stream. We provide evidence for a previously undescribed tangential dorso-septo-caudal migratory stream, with neuroblasts supported by DCX-positive fibers. Finally, we provide evidence for a commissural migration stream seemingly bound for the contralateral nucleus sphericus. Therefore, in addition to two previously known migratory streams, this study provides anatomical evidence in support for two novel migratory routes in amniotes.
Assuntos
Proteína Glial Fibrilar Ácida/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Telencéfalo/metabolismo , Animais , Movimento Celular/fisiologia , Proteínas do Domínio Duplacortina , Lagartos , Vias Neurais/metabolismo , Células-Tronco Neurais/metabolismoRESUMO
N-methyl D-aspartate (NMDA) preconditioning is evoked by the administration of a subtoxic dose of NMDA and is protective against neuronal excitotoxicity. This effect may involve a diversity of targets and cell signaling cascades associated to neuroprotection. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) such as extracellular regulated protein kinase 1/2 (ERK1/2) and p38MAPK pathways play a major role in neuroprotective mechanisms. However, their involvement in NMDA preconditioning was not yet fully investigated. The present study aimed to evaluate the effect of NMDA preconditioning on PI3K/Akt, ERK1/2, and p38MAPK pathways in the hippocampus of mice and characterize the involvement of PI3K on NMDA preconditioning-evoked prevention of seizures and hippocampal cell damage induced by quinolinic acid (QA). Thus, mice received wortmannin (a PI3K inhibitor) and 15 min later a subconvulsant dose of NMDA (preconditioning) or saline. After 24 h of this treatment, an intracerebroventricular QA infusion was administered. Phosphorylation levels and total content of Akt, glycogen synthase protein kinase-3ß (GSK-3ß), ERK1/2, and p38MAPK were not altered after 24 h of NMDA preconditioning with or without wortmmanin pretreatment. Moreover, after QA administration, behavioral seizures, hippocampal neuronal degeneration, and Akt activation were evaluated. Inhibition of PI3K pathway was effective in abolishing the protective effect of NMDA preconditioning against QA-induced seizures, but did not modify neuronal protection promoted by preconditioning as evaluated by Fluoro-Jade B staining. The study confirms that PI3K participates in the mechanism of protection induced by NMDA preconditioning against QA-induced seizures. Conversely, NMDA preconditioning-evoked protection against neuronal degeneration is not altered by PI3K signaling pathway inhibition. These results point to differential mechanisms regarding protection against a behavioral and cellular manifestation of neural damage.
Assuntos
Agonistas de Aminoácidos Excitatórios/administração & dosagem , Hipocampo/patologia , N-Metilaspartato/administração & dosagem , Doenças Neurodegenerativas/induzido quimicamente , Fosfatidilinositol 3-Quinase/metabolismo , Ácido Quinolínico/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Esquema de Medicação , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Doenças Neurodegenerativas/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fatores de TempoRESUMO
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-1ß 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.
Assuntos
Antiparkinsonianos/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/complicações , Pirróis/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/administração & dosagem , Administração Intranasal , Análise de Variância , Animais , Atorvastatina , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Transtornos Cognitivos/etiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Preferências Alimentares/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos do Humor/etiologia , Ratos , Ratos Wistar , Comportamento Social , Sacarose/administração & dosagem , Edulcorantes/administração & dosagem , Natação , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
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.
Assuntos
Derivados de Benzeno/toxicidade , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Compostos Organosselênicos/toxicidade , Proteína 25 Associada a Sinaptossoma/metabolismo , Sistema X-AG de Transporte de Aminoácidos/imunologia , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Proteína Glial Fibrilar Ácida/imunologia , Técnicas In Vitro , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Proteína 25 Associada a Sinaptossoma/imunologia , Testes de Toxicidade Aguda , Proteínas Vesiculares de Transporte de Glutamato/imunologia , Proteínas Vesiculares de Transporte de Glutamato/metabolismoRESUMO
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.
Assuntos
Astrócitos/citologia , Meio Ambiente , Hipocampo/citologia , Abrigo para Animais , Plasticidade Neuronal/fisiologia , Animais , Astrócitos/metabolismo , Proteína Glial Fibrilar Ácida/biossíntese , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , CamundongosRESUMO
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.
Assuntos
Tonsila do Cerebelo/metabolismo , Astrócitos/metabolismo , Ciclo Estral/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Proteína Glial Fibrilar Ácida/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Imuno-Histoquímica , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Ovariectomia , Progesterona/metabolismo , Progesterona/farmacologia , Ratos , Ratos Wistar , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual Animal/fisiologiaRESUMO
Using immunohistochemistry and optical densitometry, somatostatin (SOM), calcitonin gene-related peptide (CGRP), and gamma-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.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Rana catesbeiana/metabolismo , Nervo Isquiático/fisiologia , Somatostatina/metabolismo , Medula Espinal/metabolismo , Ácido gama-Aminobutírico/imunologia , Ácido gama-Aminobutírico/metabolismo , Animais , Rana catesbeiana/imunologia , Nervo Isquiático/cirurgia , Somatostatina/imunologia , Medula Espinal/citologia , Medula Espinal/imunologiaRESUMO
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.