Effects Of Gastrodin And Sodium Valproate On Synaptic Transmission And Plasticity In Rat Hippocampal CA1 Area

Lead is a well known toxin in environment,which can produce severe damage to nervous system.Lines of evidence have shown lead impaired the ability of learning and memory.Gastrodin,the main bioactive component of Tian ma,has been used in China for many years as a clinical drug.Recently,several studies have shown the cognitive-enhancing and neuroprotective effects of gastrodin.Sodium valproate (VPA) is widely used as an antiepileptic drug with a broad spectrum of anticonvulsant activity and particular efficacy in the generalized epilepsies.In spite of its wide use for many years,the mechanisms of action of VPA are still not fully understood.So far,there were few studies about effects of VPA on synaptic transmission and the data presented were not consistent.In the present study,we investigated the effects of gastrodin and VPA on synatic transmission and plasiticity by electrophysiological and biochemical methods.In addition,the neuroprotective of gastrodin on lead-induced dysfunction in rat hippocampal CA1 reigon were also investigated.The main results are as follows:1.Acute gastrodin perfusion augmented the basal synaptic transmission in a concentration-dependent manner ranging from 0.015 to 0.9 mM.This effect was unlikely due to an increase in glutamate release from presynaptic terminals since there was a significant increase in the paired pulse ratio(PPF).And this effect was not blocked by AP5,an antagonist of NMDA receptor,suggesting this effect was not mediated by NMDA receptors.Furthermore,the result about LTP showed gastrodin didn't affect the induction of LTP.2.Lead exposure significantly impaired synaptic plasticity in the hippocampal CA1 region,and the abilities of antioxidant defense system and cholinergic system; Gastrodin effectively rescued these lead-induced impairments.The results herein suggest that oxidative and cholinergic mechanisms may underlie the hippocampal effects of lead in developmental rats,in view of the protective effects of gastrodin. Thus,gastrodin may have potential therapeutic value for lead-induced impairments during human development stages.3.The effects of gastrodin on synaptic transmission and neuroal excitability in rat hippocampus were investigated by whole-cell patch clamp recordings.Perfusion with VPA,at therapeutically attainable concentrations significantly increased the frequency but not the amplitude of miniature inhibitory postsynaptic currents (mIPSCs);while did not alter both amplitude and frequency of miniature excitatory postsynaptic currents(mEPSCs).In acutely dissociated CA1 pyramidal neurons,VPA did not affect the GABA-induced currents.Additionly,we also found the frequency of action potential(AP) firing was significantly reduced and spike frequency adaptation(SFA) was significantly increased by VPA application. These results suggest that VPA presynaptically increases inhibitory synaptic activity without modifying excitatory synaptic transmission and reduces the neuronal excitability,any or all of which may contribute to its anticonvulsant action.