Relieving Effect Of Quercetin On Lead-induced Impairment Of Synaptic Plasticity In Rat Hippocampus And The Inhibitory Effect Of Natratoxin Neurotoxin On A-type K~+ Currents In Rat Dorsal Root Ganglion Neurons

Lead (Pb²⁺) is one of the most important neurotoxic metals in the environment. It has now been well established that chronic Pb²⁺ exposure in development produces deficits of learning and memory, cognitive deficits and neurobehavioral dysfunction in children and in a lot of animal species. Hippocampus is an important brain region which plays a key role in learning and memory. Long-term potentiation (LTP) in hippocampus is an activity-dependent synaptic plasticity that is believed to form the cellular basis for learning and memory. Chronic Pb²⁺ exposure in development induces impairments of synaptic plasticity in rat hippocampus. It was suggested that such deficits in LTP may underlie cognitive impairments associated with Pb²⁺ exposure. Recent studies suggest that Pb²⁺ produces impairments partly through oxidative stress. Flavonoids are a group of naturally occurring compounds widely distributed in most plants. Quercetin is the representative natural flavonoid molecule that has a long history of consumption as part of normal human diet, such as fruits, vegetables, wine and tea. As a strong antioxidant and radical scavenger, quercetin is mort potent that vitamin C, vitamin E, andβ-carotene on a molar basis. In addition, quercetin can chelate metal ions due to its catechol function site. To determine whether quercetin treatment could rescue impairments of synaptic plasticity induced by chronic Pb²⁺ exposure, we investigated the input/output functions (I/O), paired-pulse reactions (PPR) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anaesthetized rat in vivo by stimulating the lateral perforant path and recording field potentials. The results showed that the depressed I/O, PPR and long-term potentiation (LTP) of chronic Pb²⁺-exposed group were significantly increased by quercetin treatment. In addition, hippocampal Pb²⁺ concentrations of different treatment groups were measured by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results showed that hippocampal Pb²⁺ concentration was partially reduced after quercetin treatment. These findings suggest that quercetin treatment could relieve chronic Pb exposure-induced himpairment of synaptic plasticity and might be a potential therapeutic intervention to cure cognitive deficits induced by Pb²⁺.Snake venom secretory phospholipaseA2s (sPLA2s) have a lot of neurotoxic and pathological functions which are still not clearly revealed. Here we investigated the inhibitory effect of Natratoxin, a newly purified snake venom secretory phospholipaseA2s (sPLA2s) from Naja atra venom, on A-type potassium currents in media-sized (35-40 mm) neurons from acutely dissociated rat dorsal root ganglia (DRG) by conventional whole-cell voltage-clamp method. The inhibitory effect was dose dependent. For the normalized activation curves fitted by a single Boltzmann equation, there was an obvious shift to more hyperpolarized voltages with increasing concentrations of Natratoxin. The V_1/2 and the slope factor k decreased from -5.0±2.8 mV and 18.3±2.8 mV under control condition to -13.5±2.2 mV (P<0.05) and 15.4±2.0 mV (P<.05) by 10μM Natratoxin, respectively. For the normalized steady-state inactivation curves, the V_1/2 decreased from -80.5±0.9 mV under control condition to -93.0±2.6 mV (P<0.01) and the k increased from 9.3±0.9 mV under control condition to 11.6±1.8 mV (P<0.05) by 10μM Natratoxin, respectively. The curves were shifted to more hyperpolarized voltages by Natratoxin, indicating that channels were easier to be inactivated at higher concentrations of Natratoxin at any given potential. In addition, we found that the inhibitory effects of Natratoxin on A-type K⁺ currents were independent of its enzymatic activities. In conclusion, our results showed that Natratoxin caused the alteration of properties of A-type potassium currents in rat DRG neurons. These may contribute to the peripheral neurotoxic effects and nociceptive effects of snake venom sPLA2s observed in human snakebite envenomations.