RESUMO
Early degeneration of pedunculopontine nucleus (PPN) is considered part of changes that characterize premotor stages of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN in motor execution and in the development of oxidative stress events in striatal and nigral tissues in rats were evaluated. The motor performance was assessed using the beam test (BT) and the cylinder test (CT). Nigral and striatal redox balance, was studied by means of biochemical indicators such as malondialdehyde (MDA), nitric oxide (NO) and the catalase enzymatic activity (CAT EA). Lesioned rats showed fine motor dysfunction expressed both as an increase in the length (p<0.001) and deviation (p<0.001) of the traveled path and also in the time spent (p<0.01) in the circular small beam (CBS) (p<0.01) in comparison with control groups. In addition, the lesioned rats group presented a right asymmetry index greater than 0.5 which is consistent with a significant increase in the percentage of use of the right forelimb (ipsilateral to the lesion), compared with the control group (p<0.05). Biochemical studies revealed that after 48-h PPN neurotoxic injury, the CAT EA showed a significant increase in the subtantia nigra pars compacta (SNpc) (p<0.05). This significant increase of CAT EA persisted in the nigral tissue (p<0.001) and reached the striatal tissue (p<0.001) seven days after PPN injury. Also at seven days post-injury PPN, increased concentrations of MDA (p<0.01) and a tendency to decrease in the concentrations of NO in both structures (SNpc and striatum) were found. The events associated with the generation of free radicals at nigral and striatal levels, can be part of the physiological mechanisms underlying motor dysfunction in rats with unilateral PPN neurotoxic lesion.
Assuntos
Corpo Estriado/fisiologia , Atividade Motora/fisiologia , Núcleo Tegmental Pedunculopontino/fisiopatologia , Equilíbrio Postural/fisiologia , Substância Negra/fisiologia , Animais , Catalase/metabolismo , Agonistas de Aminoácidos Excitatórios/toxicidade , Membro Anterior/fisiopatologia , Lateralidade Funcional , Masculino , Malondialdeído/metabolismo , Transtornos dos Movimentos/fisiopatologia , N-Metilaspartato/toxicidade , Óxido Nítrico/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia , Núcleo Tegmental Pedunculopontino/efeitos dos fármacos , Núcleo Tegmental Pedunculopontino/patologia , Ratos WistarRESUMO
INTRODUCTION: Chronic hypoperfusion in rats produces memory and learning impairments due to permanent occlusion of commun carotid arteries (POCCA). Molecular mechanisms leading to behavioural disorders have been poorly studied. For this reason, the aim of the present study was to characterise oxidative metabolism disorders and their implications in memory and learning impairments. METHODS: Superoxide dismutase (SOD) and catalase (CAT) activities were determined in cortex, hippocampus and striatum homogenates at 24 hours and at 22 days after the lesion. Haematoxylin-eosin staining and glial fibrillary acidic protein (GFAP) immunoreactivity were performed on coronal sections. Behavioural impairments were explored using the Morris water maze (MWM). Escape latencies were determined in all behavioural studies. RESULTS: The lesion induced a significant increase (P<.01) in CAT activity in the cortex at 24 hours, while SOD activity was significantly higher (P<.01) in the cortex and hippocampus at 22 days. An intense vacuolization was observed in the cortex and striatum as a result of the lesion. A neuronal loss in the striatum and hippocampus was observed. The glial reaction increased in the cortex and striatum. Visual alterations were observed in the lesion group with the lowest evolution time (P<.001). Escape latencies, corresponding to MWM schemes for long-term and short-term memory evaluation increased significantly (P<.05) in both groups of lesioned animals. CONCLUSION: It was concluded that changes in SOD and CAT activities indicate a possible implication of oxidative imbalance in the pathology associated with chronic cerebral hypoperfusion. In addition, the POCCA model in rats is useful for understanding mechanisms by which cerebral hypoperfusion produces memory and learning impairments.
Assuntos
Isquemia Encefálica/metabolismo , Isquemia Encefálica/psicologia , Aprendizagem/fisiologia , Memória/fisiologia , Animais , Artéria Carótida Primitiva/patologia , Estenose das Carótidas/metabolismo , Estenose das Carótidas/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Motivação/fisiologia , Proteínas do Tecido Nervoso/efeitos dos fármacos , Oxirredução , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismoRESUMO
INTRODUCTION: The pedunculopontine nucleus (PPN), co-localized with the mesencephalic locomotor region, has been proposed as a key structure in the physiopathology of Parkinson's disease. OBJECTIVES: The goal of the present study was to assess if the aminoacid neurotransmitter release in the PPN is modified by the degeneration of dopaminergic cells, from substantia nigra pars compacta in 6-hydroxidopamine (6-OHDA)-lesioned rats. In addition, it was studied the aminoacid neurotransmitter release in the PPN of rats with lesion of the subthalamic nucleus by quinolinic acid (QUIN) (100 nmol) intracerebral injection. MATERIALS AND METHODS: Rats were assigned to five groups: untreated rats (I) (n = 13), 6-OHDA lesion (II) (n = 11), 6-OHDA + QUIN lesion (III) (n = 9), sham-operated (IV) (n = 10), QUIN, STN (V) lesioned (n = 9). The extracellular concentrations of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) were determined by brain microdialysis and high performance liquid chromatography (HPLC). RESULTS. GLU released in PPN from 6-OHDA lesioned rats (group II), was significantly increased in comparison with the others groups (F(4, 47) = 18.21, p < 0.001). GABA released shows significant differences between experimental groups (F(4, 45) = 12.75, p < 0.001). It was detected a higher valour (p < 0.05) in-group II. The groups III and IV exhibited intermeddle valour (p < 0.001) and groups I and IV (p < 0.001) showed the lower GABA extracellular concentrations. The infusion of artificial cerebrospinal fluid with higher potassium (100 mmol) induced an increase in the GLU and GABA released in all groups, which confirm the neuronal origin of the extracellular content. CONCLUSION: These results are in agreement with the current model of basal ganglia functioning and suggest the role of STN-PPN projection in the physiopathology of Parkinson's disease.
Assuntos
Ácido Glutâmico/metabolismo , Núcleo Tegmental Pedunculopontino/metabolismo , Substância Negra , Ácido gama-Aminobutírico/metabolismo , Adrenérgicos/farmacologia , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Química Encefálica , Dopamina/metabolismo , Ácido Glutâmico/química , Masculino , Microdiálise , Neurônios/citologia , Neurônios/metabolismo , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Núcleo Tegmental Pedunculopontino/citologia , Ratos , Ratos Wistar , Substância Negra/anatomia & histologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Ácido gama-Aminobutírico/químicaRESUMO
INTRODUCTION: Nerve growth factor (NGF) is the best characterized neurotrophic polypeptide. Initially it was postulated that alterations in the expression of NGF within its production sites may be responsible for the consistent atrophy and loss of cholinergic basal forebrain neurons in dementing illness such as Alzheimer s Disease (AD). OBJECTIVE: We analyze the NGF concentration in serum from control and patients with AD in order to elucidate something alteration in this fluid related with AD neuropathology. PATIENTS AND METHODS: We applied a twosite enzyme immunoassay to determine NGF levels in sera of patients with AD. RESULTS: Sera from Alzheimer s patients (36+/-7 pg/ml) showed slight but non significant reduction in NGF levels when compared with age related controls (66+/-18 pg/ml). On the another hand, the NGF concentrations in AD patients and control subjects to the sex were following: female AD patients showed a mean of 33.27+/-10.43 pg/ml vs 57.83+/-22 pg/ml founded in female controls, while the mean value for male AD patients was 40.87+/-12.29 pg/ml vs 37.47+/-12.28 pg/ml for the male controls. In all the cases studied, no significant differences were observed according to Student t-Test. CONCLUSIONS: Even when no significant differences were observed between controls and AD patients, the results show a tendency NGF concentration decrease in this illness. Certainly, NGF is produced not only in the forebrain but throughout the body, for this reason, more studies, including the analysis of cerebrospinal fluid would be useful to define the real relationship between NGF concentration changes in serum and AD-related changes in endogenous NGF concentrations, taking into account increasing levels by exogenous NGF administration could still be useful in maintaining the cholinergic neurons.
Assuntos
Doença de Alzheimer/metabolismo , Fator de Crescimento Neural/metabolismo , Prosencéfalo/metabolismo , Idoso , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Fator de Crescimento Neural/sangue , Fator de Crescimento Neural/líquido cefalorraquidianoRESUMO
INTRODUCTION: Under physiological conditions aerobic cells produce reactive species of oxygen. Cell survival depends on the equilibrium between the oxidation processes and the antioxidant defences. This interaction determines whether the cell suffers oxidation stress or not. Recent studies suggest that a reduced capacity for oxidation metabolism and proinflammatory states contribute to neurodegenerative changes related to age in humans. OBJECTIVE: To obtain information regarding the relation of TNF-mu to oxidation phenomena in nonhuman primates. MATERIAL AND METHODS: In this study we compare serum levels of the activity of superoxide dismutase (SOD) catalase (CAT), the levels of malonyldialdehyde (MDA) and tumor necrosis factor alpha TNF-alpha using spectrophotometric techniques in young and old nonhuman primates. RESULTS AND CONCLUSION: Our results suggest a relationship between the alterations in oxidation metabolism with the neurodegenerative changes which occur in monkeys.
Assuntos
Envelhecimento/fisiologia , Macaca/fisiologia , Estresse Oxidativo , Animais , Encéfalo/fisiologia , Catalase/sangue , Malondialdeído/sangue , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: The aetiology of the neuronal death which occurs in neurodegenerative diseases is still unknown. These disorders are of insidious onset and follow an inexorable, gradually progressive course. The best known and most frequent are Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). DEVELOPMENT: Advances in molecular genetics and neurobiochemistry towards the understanding of processes involved in cell death, suggest the association of phenomena of excito-toxicity and oxidation damage in the selective degeneration of neuronal populations, characteristic of these disorders. CONCLUSION: The evidence presented here suggests that the species reactive to oxygen (SRO) play a direct part in the aetiology and/or pathogenesis of neurodegenerative disorders, although it is still very difficult to establish whether these reactive species represent the primary etiological factor, or are toxic products secondary to tissue damage.
Assuntos
Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo/fisiologia , Envelhecimento/fisiologia , Antioxidantes/metabolismo , Morte Celular/fisiologia , Radicais Livres/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
INTRODUCTION: Genetic therapy is in itself a new type of treatment, of potential use in many neurological conditions currently considered to be resistant to conventional treatment. Great advances have been made in the construction of vectors of expression and carriers of viral genes, thus work is starting on the characterization of target cells for neuronal genetic therapy. DEVELOPMENT: As a result of advances in this field, two methods of genetic transference have evolved. One, 'in vivo', involves transfection of genetic material by means of chemical or viral agents. The 'ex vivo' variant depends on manipulation of culture cells to subsequently inject them into the host organism with a view to correcting the cell phenotype. Both methods have been used in preliminary experiments designed to test the efficacy of genetic transference for improvement of dysfunction of the nervous system. At the present time there is much experimentation with the use of genetic transference using modified cells to synthetize growth factors or key enzymes of the neurotransmission process in biomodels of Parkinsonism and Alzheimer amongst other conditions. CONCLUSIONS: Genetic therapy, as is shown in this review, has great therapeutic potential for nervous diseases which are very severe and complex. There is certainly a long way to go to perfect these techniques, particularly with regard to biological security and regulation of the element transferred. However, when it is used it will mean a major qualitative change in the treatment of nervous system disorders which are at present a cause of severe handicap and have little chance of treatment.
Assuntos
Terapia Genética/tendências , Doenças do Sistema Nervoso/terapia , Neurologia/tendências , Animais , Células Cultivadas , Humanos , Transfecção/métodosRESUMO
INTRODUCTION: The cholinergic neurones of the basal forebrain play an important part in cognitive activity and axotomy of these neurones leads to their retrograde atrophy. The nootropic drug, Cerebrolysin, can protect these neurones from neurodegeneration induced by axotomy. Oxidative damage to biomolecules often occurs in neurodegenerative processes. OBJECTIVE: To determine whether transection of the septohippocampal bundle (fimbria-fornix, FF) and administration of Cerebrolysin induce alterations in antioxidant mechanisms. MATERIAL AND METHODS: Four groups of rats were studied: Healthy, treated with physiological saline; healthy treated with Cerebrolysin (2.5 ml/kg daily for one week, intraperitoneally); FF-lesioned and pretreated with physiological saline, and with lesions and pretreated with Cerebrolysin. Twenty four hours after the lesion was produced, the activity of the enzymes glutathione S-transferase (GST), glutathione reductase (GRD) and glutathione peroxidase were measured in various cerebral areas. RESULTS: The lesion caused reduced activity of the three enzymes in the hippocampus, and also in the activity of striatal GRD. Pretreatment with Cerebrolysin did not modify the enzymes in FF-lesioned rats, but did reduce the activity of hippocampal GST in healthy rats. CONCLUSIONS: The results show the sensitivity of enzyme of the glutathione system to denervation of the hippocampus, together with a modest effect of Cerebrolysin in this experimental paradigm.
Assuntos
Aminoácidos/farmacologia , Encéfalo/enzimologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Hipocampo/cirurgia , Nootrópicos/farmacologia , Septo Pelúcido/cirurgia , Animais , Antioxidantes/metabolismo , Radicais Livres/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
INTRODUCTION AND OBJECTIVE: Parkinson's disease (PD) is characterized by a progressive, slow loss of dopaminergic neurones in the substance nigra. Although the cause of this neurone loss is unknown, at the present time many papers suggest oxidative stress (OS), secondary to dopaminergic metabolism, as an aetiopathogenic factor of PD. Therefore study of the part played by OS in this would permit the use of antioxidants (AO) as another possibility for treatment of the disease. It would also be a major step forward in the search for possible biological markers. MATERIAL AND METHODS: A study using spectrophotometric techniques was made of the serum levels of four biochemical indicators: catalase (CAT), malonyl aldehyde (MDA), phospholipase A2 (PLA2) and Vitamin C (VITC) in controls and in patients with PD. We found the average value for each of the variables studied in controls and in patients, taking AO treatment into account. RESULTS: The effect of clinical variables on serum levels of CAT, MDA, PLA2 and VITC was analyzed. It was seen that only the clinical state of Hoen and Yahr was related to the biochemical indicators. The CAT activity and VITC concentration showed statistically significant differences between patients (independently of their AO treatment) and controls. The CAT activity was significantly less in those treated with AO. The patients with PD did not all have the same degree of OS. The effect of AO treatment on plasma markers showed changes only in one subgroup of Parkinson patients. CONCLUSIONS: Our study suggests that AO treatment in this condition should be tailored to the individual patient according to the degree of OS present.
Assuntos
Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ácido Ascórbico/sangue , Biomarcadores , Catalase/sangue , Progressão da Doença , Humanos , Malondialdeído/sangue , Doença de Parkinson/enzimologia , Fosfolipases A/sangue , Fosfolipases A/metabolismo , Fosfolipases A2 , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria/métodosRESUMO
Introducción y objetivo. La enfermedad de Parkinson (EP) se caracteriza por una pérdida lenta y progresiva de las neuronas dopaminérgicas localizadas en la sustancia nigra. Aunque no se conoce la causa de la pérdida neuronal, en la actualidad es frecuente encontrar trabajos que proponen el estrés oxidativo (EO), secundario al metabolismo dopaminérgico, como factor etiopatogénico en la EP; por tanto, profundizar en el conocimiento del papel que desempeña el EO en ésta permitirá utilizar los antioxidantes (AO) como una alternativa más en el tratamiento de la enfermedad, además de constituir un paso importante en la búsqueda de posibles marcadores biológicos. Material y métodos. Se realizó un estudio de los niveles séricos de cuatro indicadores bioquímicos: catalasa (CAT), malonilaldehido (MDA), fosfolipasa A2 (PLA2) y vitamina C (VITC) en controles y pacientes con EP mediante técnicas espectrofotométricas. Se determinó la media para cada una de las variables estudiadas en controles y pacientes tomando en consideración el tratamiento AO. Resultados. Se analizó la influencia de las variables clínicas sobre los niveles séricos de la CAT, MDA, PLA2 y VITC y se observó que sólo el estadio clínico de Hoen y Yahr estaba relacionado con los indicadores bioquímicos. La actividad de la CAT y la concentración de VITC presentaron diferencias estadísticamente significativas entre pacientes (independientemente del tratamiento AO) y controles, siendo la actividad CAT significativamente menor en los tratados con AO. Todos los pacientes con EP no presentaron el mismo grado de EO; la influencia del tratamiento AO sobre los indicadores séricos sólo mostró diferencias en un subgrupo de parkinsonianos. Conclusiones. Nuestro estudio sugiere que el tratamiento AO en esta enfermedad debe ser individualizado y en concordancia con el grado de EO que presente el paciente