RESUMO
A escala mundial, la isquemia cerebral constituye una de las principales causas de muerte, por lo que los modelos animales de isquemia cerebral son extensamente usados tanto en el estudio de la pato-fisiología del fenómeno isquémico; como en la evaluación de agentes terapéuticos con posible efecto protector o regenerador. Los objetivos de este estudio fueron examinar la presencia de daño neuronal en diferentes áreas cerebrales como consecuencia del evento isquémico; así como evaluar consecuencias de este proceder sobre los procesos de memoria-aprendizaje. Los grupos de estudios incluyeron un grupo experimental de animales isquémicos, 30 ratas a las que se les ocluyó ambas arterias carótidas comunes, y un grupo control. Fue evaluada la expresión de genes isquémicos e inflamatorios por técnicas de qPCR 24 horas post lesión, la morfología del tejido cerebral en áreas de corteza, estriado e hipocampo, siete días post lesión y los procesos de memoria y aprendizaje, 12 días post lesión. Los estudios morfológicos evidenciaron que el proceder induce la muerte de poblaciones celulares en corteza, estriado e hipocampo; la isquemia modificó la expresión los genes gfap, ho-1, il-6, il-17 e ifn-γ, lo cual puede ser utilizado como un marcador de proceso isquémico temprano. Adicionalmente, el daño isquémico causó un deterioro en la memoria espacial. Esta caracterización nos permite contar con un modelo experimental donde desarrollar futuros estudios sobre la patofisiología de los eventos isquémicos y la evaluación de estrategias terapéuticas.
Cerebral ischemia is a major cause of death, for this reason animal models of cerebral ischemia are widely used to study both the pathophysiology of ischemic phenomenon and the evaluation of possible therapeutic agents with protective or regenerative properties. The objectives of this study were to examine the presence of neuronal damage in different brain areas following the ischemic event, and assess consequences of such activities on the processes of memory and learning. The study group included an experimental group ischemic animals (30 rats with permanent bilateral occlusion of the carotids), and a control group. Was evaluated gene expression and inflammatory ischemic by qPCR techniques 24h post injury, brain tissue morphology in areas of cortex, striatum and hippocampus seven days post injury and processes of memory and learning, 12 days post injury. The morphological studies showed that the procedure induces death of cell populations in cortex, striatum and hippocampus, ischemia modified gfap gene expression and ho, il-6, il-17 and ifn-γ, which can be used as a marker of early ischemic process. Additionally, the ischemic injury caused spatial memory decline. This characterization gives us an experimental model to develop future studies on the pathophysiology of ischemic events and assessing therapeutic strategies.
RESUMO
PURPOSE: To evaluate the capacity of amygdala stimulation to improve neural plasticity in animals bearing lesions of the fimbria-fornix (FF) system. METHODS: The animals were lesioned under narcosis (chloral hydrate, 420 mg/kg ip.) using a bilateral transection of the FF procedure. During the same surgery some animals were implanted with an electrode in the right basolateral amygdala (BLA) to allow the electrical stimulation of this structure. Training was carried out one week after surgery using a Morris water maze. Animals were trained in four consecutive days (8 trials/day) in the non-visible platform condition except in the fourth day in which only 4 trials were performed followed by a probe trial in which the escape platform was removed. On day 5 of training 8 trials with visible platform were performed. After each of the first 3 training days one group of animals received trains of electrical stimulation to the BLA, while control groups were not stimulated. A group of non-lesioned animals served as control. The location of the electrode was confirmed histologically after the end of the experiments. RESULTS: The learning capacity of the lesioned animals was improved by the electrical stimulation of the amygdala. The latency to find the submerged platform within this group approaches that of the non lesioned animals in the course of training (2-way ANOVA with repeated measures), while other lesioned animals continued to show severely impaired learning abilities. CONCLUSIONS: This is the first evidence that stimulating the BLA can positively influence the learning abilities of lesioned animals. Further experiments should contribute to improve the stimulation paradigms to make it more effective, if possible.
Assuntos
Tonsila do Cerebelo/fisiologia , Estimulação Encefálica Profunda/métodos , Fórnice/fisiologia , Aprendizagem em Labirinto/fisiologia , Comportamento Espacial/fisiologia , Animais , Masculino , Plasticidade Neuronal/fisiologia , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
The nerve growth factor (NGF) is known to participate in the regulation of the expression levels and activity of the choline acetyltransferase (ChAT) in the nervous system. This enzyme is sensitive to the degenerative changes found in Alzheimer's disease (AD). We compared the effectiveness of intraparenchymal (ip) and intracerebroventricular (icv) administration of the murine beta-NGF (beta-NGFm) produced in our laboratories, through the determination of the expression levels and activity of the ChAT, and the evaluation of behavioral recovery in aged rat with cognitive deficit. Our results indicated that icv infusion of beta-NGFm stimulates the expression levels of ChAT gene in the striatum of old rats. Remarkable losses in the ChAT activity were observed in the septum and striatum of old rats. Exogenous administration of beta-NGFm produced a significant increase of ChAT activity in these brain regions differentially according to the administration pathway. The behavioral studies demonstrated that the administration pathway is an important factor in order to obtain the best results for a neurorestorative treatment.
Assuntos
Colina O-Acetiltransferase/metabolismo , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/metabolismo , Corpo Estriado/metabolismo , Infusões Parenterais/métodos , Aprendizagem em Labirinto/efeitos dos fármacos , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Fatores Etários , Envelhecimento/efeitos dos fármacos , Animais , Transtornos Cognitivos/diagnóstico , Corpo Estriado/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Resultado do TratamentoRESUMO
Aging impairs amygdala-hippocampus interactions involved in hippocampal LTP. NEUROBIOL. AGING. We have recently shown that the stimulation of the basolateral nucleus of the amygdala (BLA) is able to prolong early-LTP (<4h) into late-LTP (>4h) in the dentate gyrus. To study whether aging affects this interaction, aged (24-27 months) rats were used, classified as cognitively impaired (I), or non-impaired (N) by means of their results in the Morris water maze. Paired pulses (30-90 ms interval) showed no differences among age groups. Among young controls, the early-LTP induced in the dentate gyrus by stimulation of the perforant path (PP) was prolonged in a late-LTP when the BLA was stimulated 15 min later. In aged-impaired rats the stimulation of the PP induced a reduced LTP, decaying to baseline in less than 2 h. BLA stimulation was without effect. Aged non-impaired rats showed an early-LTP identical to that of young animals; however, stimulation of the BLA showed no effect. These results suggest that deficient synaptic plasticity and memory functions in aged animals might be caused, in part by impaired mechanisms of heterosynaptic reinforcement.
Assuntos
Envelhecimento/fisiologia , Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Animais , Giro Denteado/fisiologia , Estimulação Elétrica , Potenciais Evocados/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Plasticidade Neuronal/fisiologia , Ratos , Ratos Sprague-Dawley , Sinapses/fisiologiaRESUMO
Aging affects all systems, but the brain seems to be particularly vulnerable to the action of negative, age-dependent factors. A gradual loss of memory functions is one of the earliest and most widespread consequences of brain aging. The causes for such impairment are still unclear. Long-term potentiation (LTP) is one form of neural plasticity, which has been proposed as the cellular correlate for memory. LTP is affected by aging, and such alteration might be causally related to memory dysfunction. In the present paper, we review the evidence sustaining the existence of a causal link between cognitive and LTP impairments, as well as the possible mechanisms involved. New results indicate a possible involvement of a deficient reinforcement of LTP by affective influences.