RESUMO
Brain-derived neurotrophic factor (BDNF) has been proposed as a key regulator and mediator of long-term synaptic modifications related to learning and memory maintenance. Our previous studies show that application of high-frequency stimulation (HFS) sufficient to elicit LTP at the dentate gyrus (DG)-CA3 pathway produces mossy fiber structural modifications 7 days after tetanic stimulation. In the present study, we show that acute intrahippocampal microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the DG-CA3 projection of anesthetized adult rats. Furthermore, we show that BDNF functional modifications in synaptic efficacy are accompanied by a presynaptic structural long-lasting reorganization at the hippocampal mossy fiber pathway. These findings support the idea that BDNF plays an important role as synaptic messenger of activity-dependent synaptic plasticity in the adult mammalian brain, in vivo.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Fibras Musgosas Hipocampais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carbazóis/farmacologia , Citocromos c/farmacologia , Relação Dose-Resposta à Radiação , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Alcaloides Indólicos/farmacologia , Potenciação de Longa Duração/fisiologia , Potenciação de Longa Duração/efeitos da radiação , Masculino , Ratos , Ratos Wistar , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Transmissão Sináptica/efeitos da radiaçãoRESUMO
For the taiep rat, a neurological mutant with severe astrogliosis secondary to demyelination, we have described alterations in spinal cord synaptic transmission. Asynchronous responses result from phasic action potential-derived glutamate release in this mutant. To evaluate whether this anomalous transmission is also produced in other regions of the taiep CNS and whether its nature involves a presynaptic or postsynaptic disruption, we studied the CA3-CA1 hippocampal synapses. Excitatory postsynaptic currents (EPSC) evoked by stimulation of Schaffer collaterals were recorded from CA1 pyramidal cells on picrotoxin-treated slices. Initial fast and time-locked EPSCs were evoked by conventional stimulation in both control and taiep neurons, showing similar latency and amplitude values unimodally distributed. In a high percentage of taiep neurons (47%), the initial EPSC was frequently followed by additional asynchronous synaptic currents (EPSC(ASYN)) with latencies ranging from 10 to 300 msec. As with initial EPSCs, EPSC(ASYN) were action potential dependent, sensitive to tetrodotoxin, and blocked by D-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. The occurrence probability of these events decayed monoexponentially as a function of poststimulus time. The elevation of extracellular Ca(2+) induced a reduction of amplitudes and a rate increase of EPSC(ASYN), in parallel with a reduction of paired pulse facilitation of initial EPSCs. The presynaptic fiber volley, extracellularly recorded, showed no significant differences between groups, with similar mean values of area and decay time. These findings in hippocampal circuitry suggest that, in taiep, the asynchronous evoked activity represents a rather generalized phenotype of the glutamatergic synapses and that EPSC(ASYN) seems to be determined by presynaptic alterations.
Assuntos
Potenciais Pós-Sinápticos Excitadores/genética , Hipocampo/citologia , Células Piramidais/fisiologia , Sinapses/genética , Transmissão Sináptica/genética , Animais , Animais Recém-Nascidos , Cálcio/farmacologia , Relação Dose-Resposta à Radiação , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Técnicas In Vitro , Técnicas de Patch-Clamp/métodos , Células Piramidais/efeitos da radiação , Ratos , Ratos Mutantes , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Sinapses/efeitos da radiação , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/efeitos da radiaçãoRESUMO
A comparative study between crotoxin and gamma irradiated crotoxin was performed on the indirectly evoked twitches and tetani of sciatic nerve-extensor digitorum longus muscle of rats. Crotoxin (3 to 14 microg/ml) decreased the amplitude of twitches and induced a slight tetanic fade, and irradiated crotoxin did not significantly affect either twitch amplitude or tetanic tension. Since gamma radiation reduced the neurotoxicity of crotoxin it may be useful for the production of anticrotalic serum.
Assuntos
Crotoxina/toxicidade , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/efeitos da radiação , Animais , Raios gama , Masculino , Junção Neuromuscular/fisiologia , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/efeitos da radiaçãoRESUMO
The effects of high doses of X-radiation (100 kilorads) on the neuromuscular transmission of isolated sciatic nerve-sartorius muscle preparations of the frog, as evaluated by bioelectrical characteristics, were explored. Intracellular microelectrode recordings after X-irradiation showed that the resting, excitation and action potentials of nerve fibers approaching the synaptic terminal region of the motor end-plate became lessened, and also presented a slower velocity of impulse propagation, earlier than that observed in muscle cells. After forty minutes following the irradiation period, the neuromuscular transmission became blocked, although muscle fibers still responded to direct electrical stimulation. Records taken at the motor end-plate region of muscle cells, demonstrated the presence of postsynaptic miniature end-plate potentials (m.e.p.p.'s), the sequence of which fits closely into a random Poisson distribution. X-irradiation elicited an increase of the rate of m.e.p.p.'s and induced membrane changes over fine terminal nerve branches, leading into a failure to initiate and propagate action potentials. Only as time progressed, this nerve bioelectrical impairment was accompanied by a similar one in muscle cells, associated to the inability to develop contractile tension. The increase of m.e.p.p.'s frequency due to depolarization by a high K+ concentration, of presynaptic nerve membranes of control and irradiated preparations, was reversed by a high Mg+--Ca2+--free media. However, a concentration of Mg2+, which normally reduced quantal release of acetylcholine (ACh), without altering presynaptic nerve membrane potentials, failed to modify the spontaneous basal frequency of m.e.p.p.'s, both in irradiated and control preparations. The findings of the present study suggest that the presynaptic ACh synthesis, storage, and availability for ACh liberation are not early affected by X-rays, i.e. at a time when transmission from nerve to muscle had already failed. On the contrary, the most precocius membrane changes following X-irradiation, seem related to the mechanisms underlying nerve resting, excitation, and action potentials. The smallest presynaptic nerve terminal fibers close to the motor end-plate, are the most radiosensitive portion of the myoneural junction. Indeed, their bioelectric characteristics are early affected by X-rays, resulting in a failure to generate and propagate nerve impulses which lead to a blockade of neuromuscular transmission.