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Alzheimer's disease (AD) is a progressive neurodegenerative disease that afflicts millions of people all over the world. Intracerebroventricular (ICV) injection of a sub-diabetogenic dose of streptozotocin (STZ) was established as an experimental animal model of AD. The present study was conducted to evaluate the efficacy of curcumin nanoparticles (CNs) against the behavioral, neurochemical and histopathological alterations induced by ICV-STZ. The animals were divided into: control animals, the animal model of AD that received a single bilateral ICV microinjection of STZ, and the animals protected by a daily oral administration of CNs for 6 days before the ICV-STZ injection. The animals of all groups were subjected to surgical operation on the 7th day of administration. Then the administration of distilled water or CNs was continued for 8 days. The ICV-STZ microinjection produced cognitive impairment as evident from the behavioral Morris water maze (MWM) test and induced oxidative stress in the cortex and hippocampus as indicated by the significant increases in lipid peroxidation and nitric oxide (NO) levels and the significant decrease in reduced glutathione (GSH) levels. It also produced a significant increase in acetylcholinesterase (AChE) and tumor necrosis-alpha (TNF-É) and a significant decrease in Na+,K + -ATPase. In addition, a significant increase in amino acid neurotransmitters occurred in the hippocampus, whereas a significant decrease was obtained in the cortex of STZ-induced AD rats. CNs ameliorated the behavioral, immunohistochemical and most of the neurochemical alterations induced by STZ in the hippocampus and cortex. It may be concluded that CNs might be considered as a promising therapeutic agent for the treatment of AD.
Asunto(s)
Enfermedad de Alzheimer , Curcumina , Nanopartículas , Enfermedades Neurodegenerativas , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Curcumina/farmacología , Curcumina/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Masculino , Aprendizaje por Laberinto , Estrés Oxidativo , Ratas , Ratas Wistar , Estreptozocina/toxicidadRESUMEN
OBJECTIVES: The present study aims to investigate the pathological mechanisms mediating the effect of paradoxical sleep deprivation (PSD) for 48 hr on the spontaneous recurrent seizures (SRS) stage of the pilocarpine rat model of temporal lobe epilepsy. MATERIALS AND METHODS: This was carried out through assessment of amino acid neurotransmitter levels, the main oxidative stress parameters, and the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the hippocampus. The experimental animals were divided into 4 groups: control, epileptic, PSD, and epileptic+PSD groups. RESULTS: Data indicated that PSD in epileptic rats induced a significant decrease in GSH levels. TNF-α increased significantly in the PSD group and decreased significantly in both epileptic rats and epileptic rats deprived of paradoxical sleep. PSD induced a significant increase in glutamine, glutamate, and aspartate and a significant decrease in GABA. In epileptic rats and epileptic rats deprived of PS, a significant increase in aspartate and a significant decrease in GABA and taurine were recorded. CONCLUSION: The present data suggest that exposure to PSD for 48 hr did not worsen the alterations produced in the present epileptic model. However, epileptic, PSD, epileptic + PSD groups showed a state of hyperexcitability and oxidative stress. PSD may increase the susceptibility of animals to the development of epilepsy.
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INTRODUCTION: Caffeine and nicotine are the most widely consumed psychostimulants worldwide. Although the effects of each drug alone on the central nervous system have been studied extensively, the literature on the neurochemical and electrophysiological effects of their combined treatments is scarce. The present study investigated the cortical electrophysiological and neurochemical alterations induced by acute administration of caffeine and nicotine in rats. METHODS: The rats received caffeine and nicotine at a 1-hour interval between the two treatments. RESULTS: Caffeine and nicotine administration resulted in a significant decrease in the concentrations of cortical amino acid neurotransmitters, namely glutamate, aspartate, glycine, and taurine, while γ-aminobutyric acid (GABA) significantly increased. Increased cortical lipid peroxidation and reduced glutathione and nitric oxide levels and acetylcholinesterase and Na+/K+-ATPase activities were also observed. The Electroencephalogram (EEG) showed an increase in delta frequency power band, whereas theta, beta-1, and beta-2 decreased after caffeine and nicotine treatment. CONCLUSION: These findings suggest that caffeine and nicotine adversely exacerbate their stimulant effects manifested by the EEG changes mediated by increasing cholinergic transmission and disturbing the balance between the excitatory and inhibitory amino acids leading to oxidative stress.
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The aim of the present work was to investigate the neurochemical changes induced in the cerebellum of rat model of Parkinson's disease (PD). Rats were divided into two groups; control and rat model of PD induced by the intrastriatal injection of rotenone. As compared to control, a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine were observed in the cerebellum of rat model of PD. This was associated with a significant increase in lipid peroxidation, nitric oxide and tumor necrosis factor-α and a significant decrease in reduced glutathione. A significant decrease in acetylcholinesterase and a significant increase in Na+,K+-ATPase were recorded in the cerebellum of rat model of PD. In addition the cerebellar sections from rat model of PD showed marked necrosis of Purkinje cells, irregular damaged cells, cytoplasmic shrinkage, necrosis and perineuronal vacuolation. The present results indicate that the disturbance in the balance between the excitatory and inhibitory amino acids may have a role in the pathogenesis of PD. According to the present neurochemical and histopathological changes, the cerebellum should be taken into consideration during the treatment of PD.
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Cerebelo/metabolismo , Cerebelo/patología , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Enfermedad de Parkinson Secundaria/metabolismo , Enfermedad de Parkinson Secundaria/patología , Rotenona/farmacología , Animales , Cuerpo Estriado/efectos de los fármacos , Masculino , Proteínas del Tejido Nervioso/metabolismo , Ratas , Ratas Wistar , Desacopladores/farmacologíaRESUMEN
AIMS: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease affecting the population. The present study investigates the potential therapeutic effect of cerebrolysin (CBL), as a neurotrophic factor mimic, on the behavioral and biochemical alterations induced in 6-hydroxydopamine (6-OHDA) - lesioned rats as a model of PD. MAIN METHODS: The animals were divided into 3 experimental groups; control group, Parkinsonian model group through bilateral microinjection of 6-OHDA into substantia nigra (SN) and CBL-treated group which received a daily intraperitoneal administration of CBL (2.5ml/kg) initiated 24h after induction of Parkinsonism for 21days. KEY FINDINGS: Treatment of Parkinsonian animals with CBL succeeded in restoring the midbrain and striatum dopamine levels. In addition, it normalized the increased MDA and NO levels recorded in the Parkinsonian animals and replenished the decreased level of midbrain GSH. In addition to the recorded recovery of the biochemical parameters, there was a parallel improvement in the animal's behavioral aspects. SIGNIFICANCE: The findings of the present study provide evidence for the promising therapeutic effect of CBL in the present 6-OHDA rat model of PD through counteracting oxidative stress, replenishing dopamine content and enhancing behavioral outcomes.
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Aminoácidos/uso terapéutico , Modelos Animales de Enfermedad , Oxidopamina/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Masculino , Ratas , Ratas WistarRESUMEN
Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of polycarbonated plastics and epoxy resins and line metal beverage cans. Growing evidence suggests that BPA acts directly on neuronal functions as it is lipophilic and could accumulate in the brain. The present study aims to investigate the effect of two doses of BPA (10 mg/kg for 6 and 10 weeks and 25 mg/kg for 6 weeks) on excitatory (glutamate and aspartate) and inhibitory (γ-aminobutyric acid, glycine, and taurine) amino acid neurotransmitter levels in the cortex and hippocampus. This study extends to investigate the effect of BPA on acetylcholinesterase (AchE) activity and some oxidative stress parameters in the two regions. In the cortex, a significant increase in the excitatory and a significant decrease in the inhibitory amino acids occurred after BPA (10 mg/kg for 10 weeks and 25 mg/kg for 6 weeks). This was accompanied by a significant increase in lipid peroxidation, nitric oxide, and reduced glutathione after 6 weeks of BPA (25 mg/kg). In the hippocampus, a significant increase in the excitatory and inhibitory amino acid neurotransmitters occurred after 6 weeks of BPA. Hippocampal lipid peroxidation increased significantly after BPA exposure and hippocampal reduced glutathione increased significantly after 6 weeks of BPA exposure (10 mg/kg). BPA induced a significant increase in cortical and hippocampal AchE activity. The present neurochemical changes in the cortex and hippocampus suggest that BPA induced a state of excitotoxicity and oxidative stress. This may raise concerns about the exposure of humans to BPA due to its wide applications in industry.
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Compuestos de Bencidrilo/toxicidad , Corteza Cerebral/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Animales , Compuestos de Bencidrilo/administración & dosificación , Biomarcadores/metabolismo , Química Encefálica/efectos de los fármacos , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Disruptores Endocrinos/administración & dosificación , Contaminantes Ambientales/administración & dosificación , Glutatión/agonistas , Glutatión/antagonistas & inhibidores , Glutatión/metabolismo , Hipocampo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Neuronas/metabolismo , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/metabolismo , Óxido Nítrico/agonistas , Óxido Nítrico/metabolismo , Especificidad de Órganos , Oxidación-Reducción , Fenoles/administración & dosificación , Distribución Aleatoria , Ratas Wistar , Transmisión Sináptica/efectos de los fármacos , Pruebas de Toxicidad SubcrónicaRESUMEN
Bisphenol A (BPA) is an endocrine disrupting chemical used on a wide range in industry. Several studies reported that BPA may cause cardiovascular disorders in humans and animals. The present study aims to investigate the effect of BPA on the heart of adult male rats. The rats received a daily oral administration of BPA (25 mg/kg for 6 weeks and 10 mg/kg for 6 and 10 weeks). It was found that BPA at the two studied doses induced a significant increase in malondialdehyde, and a significant decrease in catalase after 6 weeks. Moreover, a significant decrease in reduced glutathione and acetylcholinesterase (AchE) activity was observed after treatment with the two doses of BPA throughout the studied time intervals. The two doses (25 and 10 mg/kg) resulted in a significant decrease in nitric oxide (NO) levels after 6 and 10 weeks, respectively. A significant increase in body weight gain occurred in all animals after BPA treatment. These results suggest that BPA has cardiotoxic effects which are mediated by the oxidative stress resulting from the overproduction of free radicals, the deficiency of NO and the inhibition of AchE leading to cholinergic activation. The obesity promoting effect of BPA may also participate in the observed cardiovascular disturbances.