RESUMO
Brain-derived neurotrophic factor (BDNF) concentration was measured in the striatum and cortex after quinolinic acid intrastriatal lesion and transplantation of bone marrow cells (BMSC). The results showed a significant increase of the BDNF levels in the striatum and cortex of the lesioned animals and the ability of the transplanted cells to increase the levels of BDNF in both sites. This recovery of BDNF production and distribution might have beneficial effects and ameliorate the negative consequences of the striatal lesion, a mechanism of potential interest for the treatment of Huntington's disease (HD).
Assuntos
Transplante de Medula Óssea/métodos , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Ácido Quinolínico/toxicidade , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/cirurgia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/cirurgia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Age-related impairment in synaptic plasticity, like long-term potentiation (LTP), has been repeatedly reported. We had shown that late stages of LTP in the rat dentate gyrus can be modulated by emotional factors, but this is impaired by aging. In the present study we have searched for possible impairments in emotional and spatial memory tasks that may correspond to the impaired reinforcement observed at the cellular level. We have trained young and aged animals in a battery of tests: exploration (open field) object recognition, anxiety (plus maze) fear conditioning and spatial memory (Morris' water maze (MWM)). The open field, anxiety, and novelty recognition showed no age differences except a reduced velocity in aged rats. Emotional and contextual memories were preserved, but acquisition was slightly impaired. Age-dependent impairments appeared in spatial memory, evaluated in terms of latency and distance to reach the hidden escape platform in the water maze task, but these were not related with impairments in other tests, in particular there was no relation between spatial and emotional memory impairments. Age-related impairments in different paradigms were caused by different independent factors that did not correlated with each other.
Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiopatologia , Avaliação da Deficiência , Transtornos da Memória/fisiopatologia , Transtornos do Humor/fisiopatologia , Animais , Causalidade , Modelos Animais de Doenças , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Modelos Estatísticos , Transtornos do Humor/diagnóstico , Transtornos do Humor/etiologia , Ratos , Ratos WistarRESUMO
Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy considered to be the cellular basis of memory. LTP consists of an early, protein synthesis-independent phase (E-LTP) and a late phase that depends on protein synthesis (L-LTP). Application of a weak tetanus can induce E-LTP in the dentate gyrus (DG) which can be reinforced into L-LTP by direct stimulation of the basolateral amygdala (BLA) within 30 min before or after LTP induction (structural LTP-reinforcement). LTP can be depotentiated by low-frequency stimulation (LFS) to the same synaptic input if applied shortly after tetanization (<10 min). Here, we addressed the question of whether stimulation of the BLA is able to recover LTP at depotentiated synaptic inputs. We hypothesized that E-LTP can activate synaptic tags, which were then reset by depotentiation. Stimulation of the BLA thereafter could beneficially act on tag-reactivation as well as on the activation of the synthesis of plasticity-related proteins (PRPs), normally captured by the tags and thus transforming E-LTP into L-LTP. Our results show, that BLA-stimulation was not able to reactivate the resetting of tags by depotentiation in the DG of freely moving rats.
Assuntos
Tonsila do Cerebelo/fisiologia , Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Sinapses/fisiologia , Animais , Estimulação Elétrica , Masculino , Ratos , Ratos Wistar , Período Refratário Eletrofisiológico/fisiologiaRESUMO
Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy considered to be the cellular basis of memory. LTP consists of an early, protein synthesis-independent phase (E-LTP) and a late phase that depends on protein synthesis (L-LTP). In water-deprived rats E-LTP in the dentate gyrus (DG) can be reinforced into L-LTP, if the rats were allowed to drink within 15 min after E-LTP induction (behavioral LTP-reinforcement, BR). LTP can be depotentiated by low-frequency stimulation (LFS) to the same synaptic input if applied shortly after tetanization (<10 min). Here, we addressed the question of whether a BR protocol is able to recover LTP at depotentiated synaptic inputs. We show that LTP, depotentiation, LFS and BR specifically interact within one afferent input, which could be explained by the "synaptic tagging" hypothesis outlined by [Frey and Morris (1997) Nature 385:533-536]. E-LTP induced by a weak tetanus (WTET) sets tags in the activated inputs which are able to capture and to process plasticity-related proteins (PRPs) required for L-LTP, the synthesis of which was induced by BR. Synaptic tags could be reset by LFS. BR alone was unable to rescue depotentiated LTP, but the combination of BR and subsequent WTET transformed E-LTP into L-LTP. We show that LTP, LTD and behavioral stimuli alternatively and reversibly affect a single afferent input for long periods of time by LTP as well as LTD mechanisms, competing with each other under the influence of different concurrent stimuli. Affective modulation can shift the balance to one or the other. We show that the result will depend not only on the last stimulus, but on the history of previous stimuli applied to the specific input. Afferent stimuli activate alternative, but partially overlapping cascades with long-lasting consequences for the input including spaced-associative processes of "synaptic tagging" as well as "cross-tagging" which could be demonstrated in single synaptic afferents to one neuronal population in freely behaving animals.
Assuntos
Comportamento Animal/fisiologia , Giro Denteado/fisiologia , Estimulação Elétrica/métodos , Potenciação de Longa Duração/fisiologia , Motivação , Sinapses/fisiologia , Análise de Variância , Animais , Eletrodos Implantados , Masculino , Modelos Neurológicos , Neurônios Aferentes/fisiologia , Via Perfurante/fisiologia , Biossíntese de Proteínas , Ratos , Ratos Wistar , Fatores de Tempo , Privação de Água/fisiologiaRESUMO
Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy which is considered a cellular correlate of learning and memory. It has been shown that both, stimuli with emotional/motivational content and the electrical stimulation the basolateral amygdala, can modulate hippocampal LTP. The nucleus accumbens is part of the ventral striatum and is composed of two main regions: core and shell. Core and shell share a similar cellular composition, but differ in their connectivity with other brain areas. Considering that the nucleus accumbens is related to motivation and that it receives a strong projection from the basolateral amygdala, we have studied the effect of stimulating accumbens shell or core on medial perforant path-granule cells' LTP in anesthetized male Wistar rats. We found that electrical stimulation of the shell enhances the magnitude of LTP while the stimulation of the core completely prevents LTP induction. The stimulation of the accumbens shell or core alone produced no apparent, direct field potential in dentate gyrus. Additionally, the co-stimulation of the shell or core with the medial perforant path does not modify the input-output curves obtained using stimulation of the perforant path only. These results demonstrate that electrical stimulation of the accumbens shell or core has a bidirectional effect on LTP induction at the dentate gyrus.
Assuntos
Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Núcleo Accumbens/fisiologia , Anestesia , Animais , Estimulação Elétrica , Eletrodos Implantados , Potenciais Evocados/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Masculino , Neostriado/fisiologia , Núcleo Accumbens/anatomia & histologia , Ratos , Ratos WistarRESUMO
Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by subcortical, heterosynaptic afferents.
Assuntos
Vias Aferentes/lesões , Comportamento Animal/fisiologia , Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Reforço Psicológico , Vias Aferentes/cirurgia , Tonsila do Cerebelo/fisiologia , Animais , Denervação , Ingestão de Líquidos/fisiologia , Estimulação Elétrica , Eletrodos Implantados , Fórnice/lesões , Fórnice/cirurgia , Masculino , Movimento/fisiologia , Via Perfurante/fisiologia , Ratos , Ratos Sprague-Dawley , Recompensa , Privação de Água/fisiologiaRESUMO
Long-term potentiation (LTP) is considered a cellular correlate of memory processing. A short-lasting early-LTP can be prolonged into a late-L TP (>4h) by stimulation of the basolateral amygdala (BLA) or motivational behavioral stimuli in young, but not in aged, cognitively impaired rats. We measured the changes in transmitter release-induced by BLA or behavioral reinforcement-in young and aged cognitively impaired rats, after implanting a microdialysis cannula at the dentate gyrus. Samples were taken under baseline conditions and during stimulation of BLA. Rats were water deprived and tested again next day, taking samples after allowing access to water. Higher concentrations of choline, HIAA, aspartate, glutamate, and glycine were found in baseline samples from young animals compared to aged. In young animals, BLA stimulation increased the levels of ACh and reduced norepinephrine and serotonine, while behavioral reinforcement reduced the levels of glutamate and glycine. These effects were absent among aged rats, suggesting that this reduced neurochemical response might be linked to the impaired LTP-reinforcement reported previously.
Assuntos
Envelhecimento/fisiologia , Giro Denteado/metabolismo , Potenciação de Longa Duração/fisiologia , Neurotransmissores/metabolismo , Acetilcolina/metabolismo , Animais , Ácido Aspártico/metabolismo , Colina/metabolismo , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Ácido Hidroxi-Indolacético/análise , Microdiálise , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
Long-term potentiation (LTP) in the dentate gyrus can be modulated and prolonged by emotional/motivational influences when concurrently activated. A similar effect on LTP can be obtained by stimulating the amygdala, suggesting that this limbic structure might be part of the neural system involved in behavioural reinforcement. To confirm this we have performed a series of experiments in which the basolateral amygdala was either temporary inactivated by injection of lidocaine or permanently lesioned electrolytically. Both manipulations completely blocked the reinforcing effect of a motivational stimulus (drinking after 24-h deprivation) on LTP at the perforant pathway-dentate gyrus synapses, whilst leaving intact the non-reinforced potentiation. These results demonstrate that the basolateral amygdala is a key structure within the system involved in the modulatory interaction between the affective status of the animal and the mechanisms of functional plasticity.
Assuntos
Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Reforço Psicológico , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/lesões , Análise de Variância , Anestésicos Locais/farmacologia , Animais , Comportamento Animal/fisiologia , Ingestão de Líquidos , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Lidocaína/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Privação de ÁguaRESUMO
Behavioral stimuli with emotional/motivational content can reinforce long-term potentiation in the dentate gyrus, if presented within a distinct time window. A similar effect can be obtained by stimulating the basolateral amygdala, a limbic structure related to emotions. We have previously shown that aging impairs amygdala-hippocampus interactions during long-term potentiation. In this report we show that behavioral reinforcement of long-term potentiation is also impaired in aged rats with cognitive deficits. While among young water-deprived animals drinking 15 min after induction of long-term potentiation leads to a significant prolongation of potentiation, cognitively impaired aged rats are devoid of such reinforcing effects. In contrast, a slight but statistically significant depression develops after drinking in this group of animals. We suggest that an impaired mechanism of emotional/motivational reinforcement of synaptic plasticity might be functionally related to the cognitive deficits shown by aged animals.
Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Comportamento Animal , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Potenciação de Longa Duração , Reforço Psicológico , Animais , Ingestão de Líquidos/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Privação de Água/fisiologiaRESUMO
Glutathione serves the function of providing reducing equivalents for the maintenance of oxidant homeostasis, and besides it plays roles in intra- and intercellular signaling in the brain. Our purpose was to test the effects of depleting tissue glutathione by diethylmaleate (5.3 mmol/kg, intraperitoneal) on brain antioxidant metabolism, nerve growth factor levels, and cognitive performance in rats. Six hours after the treatment, glutathione level in the hippocampus dropped down to 30% of the mean value of vehicle-treated animals and glutathione peroxidase activity also declined. Twenty-four hours after the injection the values had been partially restored. Moreover, the hippocampal and cortical levels of nerve growth factor protein did not change in response to diethylmaleate treatment. Glutathione depletion did not influence the performance of animals in the step-through passive avoidance test, but impairs acquisition in the Morris water maze when given before training. However, when diethylmaleate was administered after acquisition in the same paradigm, it did not affect the retention tested at the following day. Our results suggest that glutathione status is important during acquisition, but not for retention, of spatial memory in maze tasks and they support the hypothesis of the oxidant/antioxidant equilibrium as a key piece acting in the regulation of brain function.
Assuntos
Comportamento Animal/fisiologia , Encéfalo/metabolismo , Glutationa/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Glutationa/antagonistas & inibidores , Glutationa/deficiência , Glutationa Peroxidase/antagonistas & inibidores , Habituação Psicofisiológica/efeitos dos fármacos , Habituação Psicofisiológica/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Maleatos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retenção Psicológica/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacos , Percepção Espacial/fisiologia , NataçãoRESUMO
Long-term potentiation (LTP) is a sustained increase in the efficacy of synaptic transmission, based on functional changes involving pre- and postsynaptic mechanisms, and has been considered a cellular model for learning and memory. The sulphurated tripeptide glutathione acts as a powerful antioxidant agent within the nervous system. Recent in vitro studies suggest that the cellular redox status might influence the mechanisms involved in synaptic plasticity. It is not known, however, how glutathione depletion might affect LTP. In the present study, we evaluated the input-output relationships, LTP, and paired-pulse interactions in rats with low glutathione levels induced by systemic injection of diethylmaleate. Our results in anesthetized rats show that the basic synaptic transmission between the perforant pathway and the dentate gyrus granule cells was not affected by glutathione depletion. However, in the same synapses it was not possible to induce prolonged changes in synaptic efficacy (LTP). Paired-pulse facilitation was also absent in the treated animals, suggesting an impairment of short-term synaptic interactions. These findings indicate that low content of glutathione can impair short-term and long-term mechanisms of synaptic plasticity and stress the importance of the redox balance in the normal function of brain circuitry.
Assuntos
Glutationa/metabolismo , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Animais , Estimulação Elétrica/métodos , Glutationa/antagonistas & inibidores , Injeções , Potenciação de Longa Duração/fisiologia , Maleatos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
We have recently shown that early-long-term potentiation (LTP) in the dentate gyrus can be reinforced into late LTP by stimulation of the basolateral nucleus of the amygdala [Frey et al., submitted for publication]. The pathways and mechanisms for such interactions are unclear, considering that no direct projection from the amygdala to the dentate gyrus is known. To ascertain the possible mediation of the septo-hippocampal projection we have transected the fimbria-fornix (FF) fiber system in young adult (2 months) male rats. The electrophysiological evaluation a week later showed that the lesion does not modify the effects of pre-stimulation of the basolateral amygdala (BLA) on the induction of LTP at the perforant pathway (PP)-granule cells synapses, but impairs its maintenance 1 h later. This suggests that two different pathways might mediate different aspects of the amygdala-hippocampal interactions. One seemed to be anatomically independent from the FF and might influence LTP induction; while the second, probably through the septo-hippocampal fornical projection appeared important for LTP maintenance.
Assuntos
Tonsila do Cerebelo/fisiologia , Giro Denteado/fisiologia , Fórnice/lesões , Potenciação de Longa Duração/fisiologia , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The activities of the enzymes glutathione reductase (GRD), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were studied in several rat brain areas following the aspirative transection of the septohippocampal pathway (fimbria fornix) and the administration of nerve growth factor (NGF) or cytochrome c. One group of animals remained untreated. This lesion resulted in a decreased hippocampal GRD and septal GST activities, as well as, in an increase in GPX activity from the frontal cortex, striatum, and septum. NGF prevented the lesion-induced changes in hippocampal GRD and septal GPX. These findings show that the insult resulting from the aspiration of the fimbria fornix bundle involves modifications in glutathione-related enzymes, and, therefore, in the antioxidant status of brain tissue. These changes in glutathione metabolism could be a consequence of the oxidative damage to GRD and GST proteins or represent a compensatory response of GPX to the oxidative threat The restoring effects of NGF on altered enzyme activities are possibly linked to its known neuroprotective action.
Assuntos
Encéfalo/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Hipocampo/cirurgia , Fatores de Crescimento Neural/farmacologia , Animais , Encéfalo/enzimologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: beta-NGF is a basic protein of 118 aminoacids which acts are a trophic factor for sensory and sympathetic neurons of the peripheral nervous system, and on cholinergic neurons of the anterior basal cerebrum. OBJECTIVES: In view of the functional effect of beta-HGF and its possibilities as a therapeutic agent in neurodegenerative disease, including Alzheimer's disease in this study our aim was to obtain, characterize and show the main results of the application of beta-NGFm in a model of cerebral ageing in rats with cognitive disorders. MATERIAL AND METHODS: For the obtention of beta-NGFm we followed Mobley's method as modified by Ebendal and used mouse submaxillary gland as a source of raw material. The characterization studies were carried out by application of seven techniques which allowed physicochemical characterization and demonstration of the biological activity of the product. Application of beta-NGF obtained under these conditions was carried out in a mode of cerebral ageing and the effects of treatment were assessed by conduct studies, measurement of the activity of the enzyme acetyl cholinesterase and study of neural plasticity. CONCLUSIONS: Characterization studies carried out on the beta-NGFm showed that the protein obtained consists of a mixture of molecules of beta-NGFm which are intact at their extreme N-Terminal, and molecules which have lost the octapeptide of the N-terminal position and show some modification increasing hydrophobicity. All these species were recognized immunologically by the specific antibody anti-NGFm and showed biological activity.
Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/fisiopatologia , Encéfalo/fisiologia , Modelos Animais de Doenças , Fatores de Crescimento Neural/fisiologia , Animais , Transplante de Tecido Fetal , Hipocampo/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plasticidade Neuronal/fisiologia , Ratos , Ratos Sprague-Dawley , Septo Pelúcido/embriologia , Septo Pelúcido/transplanteRESUMO
Chronic infusion of nerve growth factor (NGF, 1.2 microg/day) for 14 days to presenile rats (17 months at the beginning of treatment) that showed an initial cognitive impairment led to an improved long-term potentiation in the dentate gyrus. Both the relative increase of the slope of the population excitatory postsynaptic potential and that of the population spike were enhanced by NGF pretreatment after long-term potentiation induction at 400 Hz. The treatment was also able to increase the diminished baseline amplitude of the population spike, an effect not seen when the treatment was applied to older animals [Bergado, J., Fernández, C.I., Gómez-Soria, A., González, O., 1997a. Chronic intraventricular infusion with NGF improves LTP in old cognitively-impaired rats. Brain Res. 770, 1-9] stressing the importance of an early start of trophic therapy to achieve better results.
Assuntos
Giro Denteado/efeitos dos fármacos , Potenciais Evocados/efeitos dos fármacos , Memória/efeitos dos fármacos , Fatores de Crescimento Neural/farmacologia , Animais , Giro Denteado/fisiologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Doce ratas Sprague-Dawley fueron sujetas a la lesión de fimbria fornix (transección de la vía septohipocampal). Seis de estos animales recibieron inyecciones intraventriculares de 3 kg de factor de crecimiento nervioso (FCN) en días alternos y durante dos semanas, mientras que los otros seis recibieron citocromo c en igual esquema y dosis (controles). La actividad específica de la glutation S-transferasa (GST) se midió en el septum, el hipocampo, el estriado y la corteza frontal. Los animales tratados con FCN mostraron un incremento significativo (p < 0,002) de la actividad de la GST en el septum. No hubo diferencias entre los grupos en las otras estructuras estudiadas. Este incremento en la actividad de la GST puede estar vinculado con el efecto protector del FCN sobre la población colinérgica septal
Assuntos
Animais , Glutationa Transferase , Fatores de Crescimento Neural , RatosRESUMO
INTRODUCTION AND OBJECTIVE: The memory impairment which accompanies the aging process is a manifestation of diminished cognitive function. This is intimately related to neuropathological and biochemical changes in cholinergic areas of central nervous system (CNS). Cytokines, first described as immunoregulators, are also implied in defense reactions of the brain. Some studies on the action of IL-2 on the CNS suggest an action blocking the release of acetylcholine in the hippocampus. MATERIAL AND METHODS: We have studied the possible central neurotoxic effect of this soluble factor using the chronic intraperitoneal infusion of human recombinant IL-2 (hr-IL 2) to young and old Sprague Dawley rats. RESULTS AND CONCLUSIONS: The results do not show an in vivo action of IL-2 on the cholinergic function but are consistent with the probable role of this cytokine in the senescent cognitive impairment, in particular the age-related loss of spatial memory and/or during the evolution of neurodegenerative related process.
Assuntos
Encéfalo/efeitos dos fármacos , Interleucina-2/toxicidade , Acetilcolina/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Interleucina-2/farmacologia , Masculino , Neuroimunomodulação , Ratos , Ratos Sprague-Dawley , Comportamento Espacial/efeitos dos fármacosRESUMO
Two groups of Sprague-Dawley male rats received bilateral aspirative lesions of the fimbria fornix under chloral hydrate anesthesia. One group (n = 9) received no further treatment (lesioned). In the second group (n = 8), a piece of septal fetal tissue, obtained at day E15-16, was implanted into each lesion cavity (transplanted). A third group consisted of shamlesioned rats (controls, n = 14). Two months after the operations, a recording electrode was implanted in the hilar region of the dentate gyrus of each animal, and a bipolar stimulating electrode was implanted in the perforant path. Long-term potentiation at 400 Hz was induced and followed for two hours. FF-lesioned rats showed an impaired potentiation of the field excitatory post-synaptic potential, which rapidly declined to basal levels within 15 minutes. The transplanted rats showed a normal potentiation of this parameter, similar to that seen in the control animals. A decrease in choline acetyltransferase activity in the hippocampi of the lesioned animals showed a tendency toward recovery after septal fetal tissue transplantation. In all the dorsal hippocampal areas of the lesioned animals, acetylcholinesterase histochemistry showed an almost complete loss of enzymatic activity, which was partially restored by the transplants. The improved synaptic plasticity in the transplanted animals might be related to septal transplant-induced recovery of mnemonic functions.
Assuntos
Transplante de Tecido Encefálico/fisiologia , Giro Denteado/fisiologia , Transplante de Tecido Fetal/fisiologia , Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Acetilcolinesterase/metabolismo , Animais , Colina O-Acetiltransferase/metabolismo , Giro Denteado/enzimologia , Estimulação Elétrica , Eletrofisiologia , Potenciais Evocados/fisiologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Aged (21 months) cognitively-impaired male Sprague-Dawley rats received intraventricular infusion of nerve growth factor (NGF) or cytochrome C (Cit C) for 14 or 28 days using miniosmotic pumps and were evaluated either 1 week or 3 months after treatment. Groups of untreated young, aged-impaired and aged non-impaired rats were also evaluated. Under narcose recording and stimulating electrodes were stereotactically implanted in the dentate gyrus and the perforant path. The stimulation intensity was individually adjusted to obtain a half-maximal population spike (P) for test stimuli and a quarter-maximal for tetanization. The amplitude and latency of P and the slope (S) of the field EPSP were determined before and at 2, 5, 15, 30 and 60 min after tetanization at 400 Hz. Paired stimuli at 30 ms interval were also applied before and after tetanization. Aged, cognitively impaired rats showed an absent S potentiation and a delayed P potentiation, both in amplitude and latency, while non-impaired rats behaved like the young controls. Paired pulse inhibition showed no difference among groups before or after tetanization suggesting that the impaired potentiation is not due to an increased retroactive inhibition. NGF treatment ameliorates LTP deficits to levels equivalent to non-impaired rats, while Cit C controls showed no improvement. No differences appear among NGF treated groups, but evidence suggest that the animals evaluated 3 months after treatment developed a stronger potentiation.
Assuntos
Transtornos Cognitivos/tratamento farmacológico , Potenciação de Longa Duração/efeitos dos fármacos , Fatores de Crescimento Neural/farmacologia , Envelhecimento/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Introducción y objetivo. La afectación de memoria que se observa en el envejecimiento es una manifestación de la disminución de las funciones cognitivas con la edad, la cual está estrechamente asociada a cambios neuropatológicos y bioquímicos en áreas colinérgicas del sistema nervioso central (SNC). Las citoquinas, descritas por primera vez como moléculas inmunoreguladoras, están también implicadas en reacciones defensivas del cerebro. Estudios relacionados con la acción de la IL-2 sobre el SNC le atribuyen un efecto bloqueador sobre la secreción de acetilcolina a nivel hipocampal. Material y métodos. Hemos desarrollado un estudio dirigido a caracterizar los efectos neurotóxicos centrales de esta citoquina mediante la infusión crónica intraperitoneal de IL-2 recombinante humana (IL-2rh) en ratas jóvenes y viejas de la línea Sprague Dawley. Resultados y conclusiones. Los resultados obtenidos, aunque parciales, no parecen referir el posible efecto in vivo de la IL-2 sobre la función colinérgica central, pero si son consistentes con la implicación probable de esta citoquina en el deterioro cognitivo senescente y, de manera particular, en el deterioro de la memoria espacial asociada a la edad y/o en el curso de trastornos neurodegenerativos relacionados