RESUMO
We investigated how nitric oxide (NO) synthase inhibitor modulates muscarinic receptor expression in epileptic rats. We found that subchronic treatment (4 days) with Nω-nitro-l-arginine reduced the down-regulation of muscarinic receptors induced by pilocarpine and kainic acid in rat fronto-parietal cortex, notwithstanding the dramatic potentiation of seizures induced by both convulsants. Furthermore, functional experiments in fronto-parietal cortex slices, showed that Nω-nitro-l-arginine reduces the down-regulating effect of pilocarpine on carbachol-induced phosphoinositol hydrolysis. Finally, Nω-nitro-l-arginine greatly potentiated the induction of basic fibroblast growth factor (FGF2) by pilocarpine. These data suggest a potential role of NO in a regulatory feedback loop to control muscarinic receptor signal during seizures. The dramatic potentiation of convulsions by NO synthase inhibitors in some animal models of seizures could derive from preventing this feedback loop.
Assuntos
Ácido Caínico/toxicidade , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Pilocarpina/toxicidade , Receptores Muscarínicos/metabolismo , Convulsões/enzimologia , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inibidores Enzimáticos/farmacologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Ácido Caínico/antagonistas & inibidores , Masculino , Óxido Nítrico Sintase/metabolismo , Técnicas de Cultura de Órgãos , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/enzimologia , Pilocarpina/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamenteRESUMO
BACKGROUND: Peroxidation of lipid (LPO) membrane and cholesterol metabolism have been involved in the physiopathology of many diseases of aging brain. Therefore, this prospective animal study was carried firstly to find out the correlation between LPO in posterior brain and plasmatic cholesterol along with lipoprotein levels after chronic intoxication by aluminium chloride (AlCl3). Chronic aluminum-induced neurotoxicity has been in fact related to enhanced brain lipid peroxidation together with hypercholesterolemia and hypertriglyceridemia, despite its controversial etiological role in neurodegenerative diseases. Secondly an evaluation of the effectiveness of fenugreek seeds in alleviating the engendered toxicity through these biochemical parameters was made. RESULTS: Oral administration of AlCl3 to rats during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via the drinking water) enhanced the levels of LPO in posterior brain, liver and plasma together with lactate dehydrogenase (LDH) activities, total cholesterol (TC), triglycerides (TG) and LDL-C (Low Density Lipoproteins) levels. All these parameters were decreased following fenugreek seeds supplementation either as fenugreek seed powder (FSP) or fenugreek seed extract (FSE). A notable significant correlation was observed between LPObrain and LDL-C on one hand and LDHliver on the other hand. This latter was found to correlate positively with TC, TG and LDL-C. Furthermore, high significant correlations were observed between LDHbrain and TC, TG, LDL-C, LPObrain as well as LDHliver. CONCLUSION: Aluminium-induced LPO in brain could arise from alteration of lipid metabolism particularly altered lipoprotein metabolism rather than a direct effect of cholesterol oxidation. Fenugreek seeds could play an anti-peroxidative role in brain which may be attributed in part to its modulatory effect on plasmatic lipid metabolism.
Assuntos
Peroxidação de Lipídeos , Lipídeos/sangue , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Lobo Parietal/metabolismo , Extratos Vegetais/farmacologia , Lobo Temporal/metabolismo , Cloreto de Alumínio , Compostos de Alumínio , Animais , Glicemia , Cloretos , Cromatografia Líquida de Alta Pressão , Feminino , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/uso terapêutico , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/enzimologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Wistar , Sementes/química , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/enzimologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Trigonella/químicaRESUMO
Matrix metalloproteases (MMPs) degrade or modify extracellular matrix or membrane-bound proteins in the brain. MMP-2 and MMP-9 are activated by treatments that result in a sustained neuronal depolarization and are thought to contribute to neuronal death and structural remodeling. At the synapse, MMP actions on extracellular proteins contribute to changes in synaptic efficacy during learning paradigms. They are also activated during epileptic seizures, and MMP-9 has been associated with the establishment of aberrant synaptic connections after neuronal death induced by kainate treatment. It remains unclear whether MMPs are activated by epileptic activities that do not induce cell death. Here we examine this point in two animal models of epilepsy that do not involve extensive cell damage. We detected an elevation of MMP-9 enzymatic activity in cortical regions of secondary generalization after focal seizures induced by 4-aminopyridine (4-AP) application in rats. Pro-MMP-9 levels were also higher in Wistar Glaxo Rijswijk (WAG/Rij) rats, a genetic model of generalized absence epilepsy, than they were in Sprague-Dawley rats, and this elevation was correlated with diurnally occurring spike-wave-discharges in WAG/Rij rats. The increased enzymatic activity of MMP-9 in these two different epilepsy models is associated with synchronized neuronal activity that does not induce widespread cell death. In these epilepsy models MMP-9 induction may therefore be associated with functions such as homeostatic synaptic plasticity rather than neuronal death.
Assuntos
Epilepsia/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia , 4-Aminopiridina , Animais , Comportamento Animal , Morte Celular , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Lobo Frontal/enzimologia , Homeostase , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Lobo Parietal/enzimologia , Bloqueadores dos Canais de Potássio , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Tálamo/enzimologiaRESUMO
Stress is a part of daily life. However, molecular mechanisms underlying the activation of limbic-hypothalamic-pituitary-adrenal (LHPA) axis remains unknown. In this study, we explored whether activation of the mitogen-activated kinase kinase 4 (MKK4)-c-Jun-N-terminal kinase (JNK) signaling pathway may play a role in the activation of the LHPA axis. We found that forced-swim stress induced elevation of activated MKK4 in the hippocampal formation, amygdala, and hypothalamus. Unlike MKK4, a high basal level of JNK activity is present in many brain areas of unstressed mice. Forced-swim stress significantly elevated JNK activity in the hypothalamus and amygdala and, to a lesser extent, in the cortex, CA1 and CA3 regions, and the dentate gyrus. To further investigate the role of MKK4 and JNK in induction of stress responses, we investigated whether a different stress, namely, restraint stress, induced activation of MKK4 or JNK in the brain. We found that restraint stress also induced elevation of activated MKK4 and JNK in the hippocampal formation, amygdala, and hypothalamus. Because MKK4 and JNK were activated within 5 min following stress, we propose that the MKK4-JNK signaling may be an early neural event in the initiation of neuroendocrine, autonomic and behavioral stress responses.
Assuntos
Encéfalo/enzimologia , MAP Quinase Quinase 4 , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Fisiológico/enzimologia , Tonsila do Cerebelo/enzimologia , Animais , Tronco Encefálico/enzimologia , Giro Denteado/enzimologia , Ativação Enzimática/fisiologia , Hipotálamo/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lobo Parietal/enzimologia , Tálamo/enzimologiaRESUMO
Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition.
Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Carbamatos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Indanos/farmacologia , Fenilcarbamatos , Piperidinas/farmacologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Carbamatos/uso terapêutico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/enzimologia , Inibidores da Colinesterase/uso terapêutico , Donepezila , Relação Dose-Resposta a Droga , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Humanos , Indanos/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/enzimologia , Piperidinas/uso terapêutico , Reprodutibilidade dos Testes , Rivastigmina , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/enzimologia , Tomografia Computadorizada de EmissãoRESUMO
Melatonin and somatostatin are known to exert similar effects on locomotor activity. We have previously demonstrated that acute melatonin treatment regulates somatostatin receptor function in the rat frontoparietal cortex. However, the effects of subchronic and chronic melatonin treatment on the somatostatin receptor-G protein-adenylyl cyclase system in the rat frontoparietal cortex are unknown. Melatonin was administered subcutaneously at a daily dose of 25 microg/kg for 4 days, 1 wk or 2 wk. Twenty-four hours after the last injection, the animals were sacrificed. Melatonin did not alter the somatostatin-like immunoreactivity content in the frontoparietal cortex from control and melatonin-treated rats during any of the previously indicated periods. Four days of melatonin administration induced both an increase in the number of [(125)I]-Tyr11-somatostatin receptors and a decrease in the affinity of somatostatin for its receptors in frontoparietal cortical membranes. The increased number of somatostatin receptors in the melatonin-treated rats was associated with an increased capacity of somatostatin to inhibit basal and forskolin-stimulated adenylyl cyclase activity. Melatonin administration for 4 days induced a higher adenylyl cyclase activity both under basal conditions and after direct stimulation of the enzyme with forskolin. No significant differences were observed in the function of Gi proteins in the 4-day melatonin-treated rats. Western blot analyses showed that the 4-day melatonin treatment reduced Gialpha(2) levels, without altering the amount of Gialpha(1). These melatonin-induced changes reverted to control values after 7 or 14 days of treatment. Altogether, the present findings suggest that subchronic melatonin treatment modulates the somatostatin receptor/effector system in the rat frontoparietal cortex.
Assuntos
Adenilil Ciclases/metabolismo , Lobo Frontal/enzimologia , Melatonina/farmacologia , Lobo Parietal/enzimologia , Somatostatina/metabolismo , Animais , Colforsina/farmacologia , Lobo Frontal/efeitos dos fármacos , Guanilil Imidodifosfato/farmacologia , Imidazóis/farmacologia , Melatonina/administração & dosagem , Lobo Parietal/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Somatostatina/efeitos dos fármacos , Receptores de Somatostatina/metabolismoRESUMO
In Alzheimer's disease (AD), loss of cortical and hippocampal choline acetyltransferase (ChAT) activity has been correlated with dementia severity and disease duration, and it forms the basis for current therapies. However, the extent to which reductions in ChAT activity are associated with early cognitive decline has not been well established. We quantified ChAT activity in the hippocampus and four cortical regions (superior frontal, inferior parietal, superior temporal, and anterior cingulate) of 58 individuals diagnosed with no cognitive impairment (NCI; n = 26; mean age 81.4 +/- 7.3 years), mild cognitive impairment (MCI; n = 18; mean age 84.5 +/- 5.7), or mild AD (n =14; mean age 86.3 +/- 6.6). Inferior parietal cortex ChAT activity was also assessed in 12 subjects with end-stage AD (mean age 81.4 +/- 4.3 years) and compared to inferior parietal cortex ChAT levels of the other three groups. Only the end-stage AD group had ChAT levels reduced below normal. In individuals with MCI and mild AD, ChAT activity was unchanged in the inferior parietal, superior temporal, and anterior cingulate cortices compared to NCI. In contrast, ChAT activity in the superior frontal cortex was significantly elevated above normal controls in MCI subjects, whereas the mild AD group was not different from NCI or MCI. Hippocampal ChAT activity was significantly higher in MCI subjects than in either NCI or AD. Our results suggest that cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation. Thus, the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss. Of importance, the cholinergic system is capable of compensatory responses during the early stage of dementia. The upregulation in frontal cortex and hippocampal ChAT activity could be an important factor in preventing the transition of MCI subjects to AD.
Assuntos
Doença de Alzheimer/metabolismo , Colina O-Acetiltransferase/metabolismo , Transtornos Cognitivos/metabolismo , Lobo Frontal/enzimologia , Hipocampo/enzimologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Fibras Colinérgicas/enzimologia , Fibras Colinérgicas/patologia , Transtornos Cognitivos/patologia , Feminino , Lobo Frontal/patologia , Hipocampo/patologia , Humanos , Masculino , Testes Neuropsicológicos , Lobo Parietal/enzimologia , Lobo Parietal/patologia , Lobo Temporal/enzimologia , Lobo Temporal/patologiaRESUMO
Patients with parkinsonism-dementia complex (PDC) of Guam showed moderate loss of choline acetyl transferase activity in the midfrontal and inferior parietal cortex, and severe loss in the superior temporal cortex. This deficit was similar to that seen in Alzheimer's disease and less severe than Lewy body disease. Thus, cholinergic deficits in the neocortex might contribute to some of the cognitive alterations in PDC of Guam.
Assuntos
Colina O-Acetiltransferase/metabolismo , Neocórtex/enzimologia , Doença de Parkinson/metabolismo , Acetilcolina/metabolismo , Idoso , Doença de Alzheimer/metabolismo , Gânglios da Base/enzimologia , Feminino , Lobo Frontal/enzimologia , Guam , Humanos , Doença por Corpos de Lewy/metabolismo , Masculino , Lobo Parietal/enzimologia , Terminações Pré-Sinápticas/metabolismo , Lobo Temporal/enzimologiaRESUMO
In eukaryotic cells, cAMP regulates many different cellular functions. Its effects are in most cases mediated by cAMP-dependent protein kinases. These consist of two regulatory and two catalytic subunits. In mammals, four different isoforms of cAMP-dependent protein kinases regulatory subunits have been characterized (RIalpha and beta, RIIalpha and beta). These four isoforms show a high level of homology and slightly different biochemical properties. In addition to biochemical properties, a different anatomical distribution of the regulatory isoforms may contribute to determine the specificity of diverse cAMP effects. By immunohistochemistry, the distribution of the detergent-insoluble fraction of RIbeta isoform has been examined in rat and mouse brain. Biochemical fractionation shows that a large fraction of both RIalpha and RIbeta isoforms is bound to the cytoskeleton. RIbeta labelling can be observed only in few locations: Purkinje cells, olfactory mitral cells, lateral thalamic neurons, superior olivary complex neurons. These cell populations are involved in the so called Purkinje cell degeneration. On the other hand, RIalpha aggregates have a more widespread distribution, in brain areas involved in visceroemotional control. At the subcellular level, these two subunits show a different pattern of labelling: in most cells a sharply defined clustered labelling is observed for RIalpha isoforms, while the RIbeta isoform presents a weaker, diffuse intracytoplasmic distribution. Competition experiments point to the presence of, as yet unidentified, different and selective anchoring proteins for the two similar RIalpha and beta isoforms. It is suggested that, as is the case for structural proteins, a different supramolecular organization of similar regulatory proteins may be crucial in order to fulfill different functions.
Assuntos
Encéfalo/enzimologia , Proteínas Quinases Dependentes de AMP Cíclico/análise , Proteínas do Tecido Nervoso/análise , Sequência de Aminoácidos , Animais , Ligação Competitiva , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico , Subunidade RIbeta da Proteína Quinase Dependente de AMP Cíclico , Detergentes/farmacologia , Técnica Indireta de Fluorescência para Anticorpo , Substâncias Macromoleculares , Masculino , Camundongos , Dados de Sequência Molecular , Octoxinol/farmacologia , Transtornos do Olfato/enzimologia , Bulbo Olfatório/enzimologia , Mucosa Olfatória/enzimologia , Núcleo Olivar/enzimologia , Lobo Parietal/enzimologia , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Isoformas de Proteínas/análise , Subunidades Proteicas/análise , Células de Purkinje/enzimologia , Ratos , Solubilidade , Técnicas Estereotáxicas , Frações Subcelulares/enzimologia , Tálamo/enzimologia , Sulfato de Zinco/toxicidadeRESUMO
Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients. Item scores from the Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination (MMSE) from 389 patients with probable Alzheimer's disease were submitted to principal component analysis with orthogonal rotation. The optimal solution identified four factors that reflected the cognitive domains of attention/registration, verbal fluency/reasoning, graphomotor/praxis and recent memory. A subgroup of patients was identified for whom both the MDRS and the MMSE had been administered within the 12 months before death. Scores were assigned to these patients for the four factors. These cognitive-domain scores were then correlated with postmortem choline acetyltransferase (ChAT) activity in the medial frontal cortex, inferior parietal cortex, and hippocampus. ChAT activity in both the medial frontal and the inferior parietal cortex significantly correlated with scores on the graphomotor/praxis factor. Medial frontal ChAT also correlated significantly with the attention/registration scores. Hippocampal ChAT correlated significantly only with recent memory scores. These results are consistent with current animal research regarding the effect of selective cholinergic lesions on behavior.
Assuntos
Doença de Alzheimer/fisiopatologia , Colina O-Acetiltransferase/metabolismo , Transtornos Cognitivos/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Análise Fatorial , Feminino , Lobo Frontal/enzimologia , Lobo Frontal/patologia , Hipocampo/enzimologia , Hipocampo/patologia , Humanos , Masculino , Lobo Parietal/enzimologia , Lobo Parietal/patologia , Análise de RegressãoRESUMO
The effect of dietary red bell pepper (Capsicum annuum L.) on learning performance was studied in the senescence-accelerated mouse (SAM). An experimental diet, which contained 20% (w/w) lyophilized powder of red bell pepper, was fed to SAMP8 mice. The mice that received the experimental diet showed much better acquisition in passive avoidance tasks as compared with a control group given a common diet. This indicated that the dietary ingestion of red bell pepper ameliorated the learning impairment in SAMP8.
Assuntos
Envelhecimento , Capsicum , Dieta , Aprendizagem , Plantas Medicinais , Animais , Antioxidantes , Aprendizagem da Esquiva , Peso Corporal , Encéfalo/enzimologia , Carotenoides/análogos & derivados , Colina O-Acetiltransferase/metabolismo , Hipocampo/enzimologia , Luteína , Masculino , Camundongos , Lobo Parietal/enzimologia , XantofilasRESUMO
To investigate the toxicity of beta-amyloid protein, a component of the senile plaques in Alzheimer's disease, it was infused into the cerebral ventricle of rats for 14 days by a mini-osmotic pump. Performances in the water maze and passive avoidance tasks in beta-amyloid protein-treated rats were impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after the cessation of the infusion. However, the learning impairment was recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after the cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Furthermore, beta-amyloid protein altered the staining in the nuclei of hippocampal cells for only 2 weeks after the cessation. These results suggest that beta-amyloid protein produces some damage in the central nervous system in vivo.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Colina O-Acetiltransferase/antagonistas & inibidores , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/enzimologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Proteína Glial Fibrilar Ácida/análise , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/ultraestrutura , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Degeneração Neural/efeitos dos fármacos , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/enzimologia , Ratos , Ratos WistarRESUMO
Alterations in cholinergic function due to prolonged ethanol exposure (up to 9 months) were assessed by choline acetyltransferase (ChAT) activity and high-affinity choline uptake (HAChU) in three brain regions of the Long-Evans rat: frontal cortex, parietal cortex, and region of the nucleus basalis of Meynert (NbM). No statistically significant changes were found in ChAT activity in the 3-month group; however, ChAT activity was decreased in both the frontal cortex (-32%) and NbM region (-22%) after 6 months of ethanol exposure. ChAT activity in the parietal cortex was increased 30% after 6 months. Nine months of exposure significantly decreased ChAT activity in all three brain regions. No significant differences were observed in high-affinity choline uptake after 3 months of ethanol exposure. However, after 6 months of ethanol exposure HAChU was decreased to 51% of control values in the frontal cortex. There was a simultaneous increase in HAChU to 43% and 178% of control values in the NbM and parietal cortex, respectively. However, choline uptake was significantly decreased in the frontal cortex and NbM region after 9 months of exposure. The results indicate a neurotoxic effect of prolonged intake of ethanol on the basal forebrain cholinergic projection system, which may cause impairment of cholinergic innervation of target areas of the basal nucleus complex.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Encéfalo/efeitos dos fármacos , Sistema Nervoso Parassimpático/efeitos dos fármacos , Animais , Encéfalo/enzimologia , Química Encefálica/efeitos dos fármacos , Colina/metabolismo , Colina O-Acetiltransferase/metabolismo , Depressão Química , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Masculino , Sistema Nervoso Parassimpático/enzimologia , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/enzimologia , Ratos , Ratos Wistar , Substância Inominada/efeitos dos fármacos , Substância Inominada/enzimologia , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Rats subjected to a mild to moderate fluid percussion injury exhibit memory deficits that are similar to rats that have received lesions of the septohippocampal system. Because the cholinergic system plays a major role in septohippocampal function, we studied the kinetics of the synthetic enzyme for acetylcholine, choline acetyltransferase (ChAT), at 1 h, 24 h, or 5 days after a fluid percussion injury. Decreases in ChAT activity were found in the dorsal hippocampus (25%), frontal (32%), and temporal (23%) cortices 1 h after injury. In the parietal cortex, a greater than 50% increase in ChAT activity was observed at all time intervals assessed. At 5 days after TBI, there was an 18% increase in ChAT activity in the medial septal area. These data provide evidence that a mild to moderate fluid percussion injury produces changes in the cholinergic system in brain areas related to memory.
Assuntos
Lesões Encefálicas/enzimologia , Encéfalo/enzimologia , Colina O-Acetiltransferase/metabolismo , Análise de Variância , Animais , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Cerebelo/enzimologia , Córtex Entorrinal/enzimologia , Lobo Frontal/enzimologia , Hipocampo/enzimologia , Cinética , Masculino , Memória/fisiologia , Lobo Occipital/enzimologia , Especificidade de Órgãos , Lobo Parietal/enzimologia , Ratos , Ratos Sprague-Dawley , Lobo Temporal/enzimologia , Fatores de TempoRESUMO
We report that NO synthase activity, as expressed by citrulline and nitrite formation in brain homogenates, is decreased in 24-month old in comparison to 3-month old rats. In particular, a Ca(++)-dependent NO synthase activity was detected in homogenates obtained from cortical, hippocampal, cerebellar and lower brain stem slices from both 3- and 24 month-old rats. The amount of citrulline generated from L-arginine was significantly decreased in the hippocampus and lower brain stem by 40 and 48%, respectively. No changes were observed in NO synthase activity in cortical and cerebellar homogenates. Thus, the L-arginine-NO pathway seems to be impaired in selected areas of rat brain and this may contribute to the understanding of pathophysiological mechanisms underlying age-related cerebral disorders.
Assuntos
Envelhecimento/metabolismo , Encéfalo/enzimologia , Óxido Nítrico Sintase/metabolismo , Animais , Encéfalo/crescimento & desenvolvimento , Tronco Encefálico/enzimologia , Cálcio/farmacologia , Cerebelo/enzimologia , Citrulina/metabolismo , Lobo Frontal/enzimologia , Hipocampo/enzimologia , Técnicas In Vitro , Masculino , Nitritos/metabolismo , Especificidade de Órgãos , Lobo Parietal/enzimologia , Ratos , Ratos WistarRESUMO
The patterns of histochemical staining for acetylcholinesterase (AChE) activity in the macaque thalamus were analyzed and compared with the distribution of cells and terminals labeled from injections of axonal tracers in the dorsolateral and orbital prefrontal cortex, in area 7a of the posterior parietal cortex and in the polysensory cortex of the superior temporal sulcus. AChE histochemistry is very useful in delineating the thalamic nuclei connected with the association cortex and in uncovering thalamic subdivisions that are barely evident on cytoarchitectonic grounds. Moreover, AChE activity reveals previously unrecognized heterogeneities within several thalamic nuclei, like the ventral anterior (VA), where a new ventromedial subdivision (VAvm) is described, the medial pulvinar (PulM) or the mediodorsal nucleus (MD). In this nucleus three distinct chemical domains are present: the medial, ventral and lateral sectors characterized by low, moderate and high AChE activities, respectively. The staining pattern of the lateral sector is markedly heterogeneous with patches of intense AChE activity surrounded by a moderately stained matrix. The MD medial sector is connected with the orbitofrontal cortex, whereas the AChE-rich patches in the lateral sector are selectively connected with the dorsolateral prefrontal, parietal and temporal association cortices. In the PulM, a dorsomedial AChE-rich patch is selectively connected with the orbitofrontal cortex, whereas the surrounding territory, which shows moderate AChE activity, is preferentially connected with the parietal and temporal cortices. Chemically specific domains in the anterior, ventral anterior, midline, and intralaminar thalamic nuclei are also connected with the examined association cortices. These findings indicate that the topographic patterns of the thalamo-cortical connections of primate association areas conform to the chemical architecture of the thalamus. This implies that because each cortical area is connected to a particular set of thalamic regions, the influence of the thalamus on cortical function is exclusive for each area, highly diverse among the various association areas, and subject to a wide range of modulation at the thalamic level.
Assuntos
Acetilcolinesterase/metabolismo , Córtex Cerebral/enzimologia , Tálamo/enzimologia , Animais , Biomarcadores , Córtex Cerebral/citologia , Lobo Frontal/citologia , Lobo Frontal/enzimologia , Histocitoquímica , Peroxidase do Rábano Silvestre , Macaca nemestrina , Vias Neurais/citologia , Vias Neurais/enzimologia , Lobo Parietal/citologia , Lobo Parietal/enzimologia , Lobo Temporal/citologia , Lobo Temporal/enzimologia , Núcleos Talâmicos/anatomia & histologia , Núcleos Talâmicos/enzimologia , Tálamo/anatomia & histologia , Tálamo/citologia , Conjugado Aglutinina do Germe de Trigo-Peroxidase do Rábano Silvestre , Aglutininas do Germe de TrigoRESUMO
A defect in energy metabolism may play a role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. In the present study, we examined the activities of the enzymes that catalyze oxidative phosphorylation in frontal, temporal, parietal, and occipital cortex from Alzheimer's disease patients and age-matched controls. Complex I and complex II-III activities showed a small decrease in occipital cortex, but were unaffected in the other cortical areas. The most consistent change was a significant decrease of cytochrome oxidase (complex IV) activity of 25-30% in the four cortical regions examined. These results provide further evidence of a cytochrome oxidase defect in Alzheimer's disease postmortem brain tissue. A deficiency in this key energy-metabolizing enzyme could lead to a reduction in energy stores and thereby contribute to the neurodegenerative process.
Assuntos
Doença de Alzheimer/enzimologia , Córtex Cerebral/enzimologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Córtex Cerebral/ultraestrutura , Complexo II de Transporte de Elétrons , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético , Lobo Frontal/enzimologia , Humanos , Mitocôndrias/enzimologia , Complexos Multienzimáticos/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Lobo Occipital/enzimologia , Oxirredutases/metabolismo , Lobo Parietal/enzimologia , Succinato Desidrogenase/metabolismo , Lobo Temporal/enzimologiaRESUMO
In this work, we have described decreases of pGlu-peptidase I activity, detected using pGlu-beta-naphtylamide as substrate, from 9 to the 20 days after birth in five brain areas. In addition, we have found sexual differences in the enzyme activity in the hypothalamic-pituitary axis in all ages investigated. pGlu-peptidase cleaves the pGlu-aminoacid bond of several neuropeptides such as thyroliberin, luliberin and neurotensin. The decrease in the activity of pGlu-peptidase coincidents with the increases observed in brain thyroliberin concentration and the decreases in His-Pro diketopiperazine. It is suggested that this enzyme could play a part in the normal development of the rat brain.
Assuntos
Hipotálamo/enzimologia , Hipotálamo/fisiologia , Piroglutamil-Peptidase I/metabolismo , Ratos Sprague-Dawley/fisiologia , Fatores Etários , Animais , Feminino , Lobo Frontal/enzimologia , Lobo Frontal/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Neurotensina/metabolismo , Lobo Occipital/enzimologia , Lobo Occipital/fisiologia , Lobo Parietal/enzimologia , Lobo Parietal/fisiologia , Hipófise/enzimologia , Hipófise/fisiologia , Ratos , Fatores Sexuais , Hormônio Liberador de Tireotropina/metabolismoRESUMO
Changes in the level of glutamine synthetase (GS), an enzyme mainly located in astrocytes, were investigated in rat brain after deprivation of paradoxical sleep (PSD) and during recovery. An immunotitration method was used to evaluate the relative level of GS in brain tissue. At the end of a 24 h PSD, a significant increase in GS protein was observed both in the frontoparietal cortex (CX) and in the locus coeruleus area (LC). Four hours later during recovery, the level of GS protein returned to normal level in the CX but fell below control levels in the LC. In contrast, in the CX, the level of glial fibrillary acidic protein, an astroglial marker, did not change after PSD or during recovery. GS mRNA was quantified in the entire cortex by northern blot hybridization using of an oligonucleotidic GS-cDNA probe. We observed an increase in the GS mRNA level in the cortex of PSD rats of the same magnitude as the increase in GS protein. Both GS mRNA and GS protein tended to return to control values 4 h later during recovery. These results are discussed with particular attention to stress effects and possible physiological mechanisms regarding the regulation of amino acid levels by neurotransmitters during prolonged waking or neuronal excitation.
Assuntos
Encéfalo/enzimologia , Glutamato-Amônia Ligase/metabolismo , Privação do Sono/fisiologia , Sono REM/fisiologia , Animais , Córtex Cerebral/metabolismo , Corticosterona/sangue , Lobo Frontal/enzimologia , Proteína Glial Fibrilar Ácida/metabolismo , Glutamato-Amônia Ligase/genética , Masculino , Lobo Parietal/enzimologia , RNA Mensageiro/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Rats received a unilateral lesion of the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid. Starting 2 weeks after the lesion, the animals were treated with nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) by intraparenchymal infusion of 3 micrograms per day for 4 weeks. Lesioned control animals received a similar amount of cytochrome c. The activity of choline acetyltransferase (ChAT) in the frontal neocortex was significantly reduced by the lesion (-39%). However, the intraparenchymal treatment with NGF or BDNF did not affect cortical ChAT activity. The number of p75 NGF receptor-immunoreactive neurons in the NBM was significantly decreased (-49%) by the lesion and was not affected by NGF or BDNF. The size of the remaining neurons was significantly increased by NGF (+32%), but not by BDNF (+12%). Similarly, in situ hybridization showed enhanced expression of the p75 NGF receptor following treatment with NGF, but not with BDNF. These results suggest that although BDNF occurs in the target area of cholinergic NBM neurons, its effects on these neurons are less pronounced than those of NGF.