Taurine On Prenatal And Perinatal Lead Exposure Causes Rat Hippocampal Synaptic Plasticity-damage Repair

Taurine (2-aminoethanesulfonic acid) is one of the most abundant free amino acids in the central nervous system. In many mammals, its concentration even exceeds that of glutamate during ontogenic development. This simple sulfonic acid has been thought to have multiple roles in the brain. Taurine is an osmoregulator and neuromodulator, also being essential for the developmental and survival for neural cells. Numerous studies have proposed that taurine can protect neural cells in some pathological conditions. In physiological conditions, taurine is highly cumulated in neurons at concentration of 5-70 mM, and is released in high amounts under various pathologic conditions such as ischemia or anoxia and seizures. In addition, taurine is a known regulator of calcium homeostasis and seems to have a promising antioxidant effect against oxidative damages. As an inhibitory neuromodulator, taurine can activate glycine receptors and GABAa receptors. Most important, taurine at high concentrations may induce long-lasting potentiation of field excitatory postsynaptic potentials in the hippocampal and brain slices. This indicates that taurine plays a role in modulation of synaptic transmission and in synaptic plasticity.Previous study has demonstrated that taurine is released from neurons in the upper dorsal horn layers, an area known to process nociceptive input. Systemic and intrathecal administration of taurine is analgesic in some acute pain tests. It has been suggested that taurine may be a natural neuroprotectant against input excitotoxicity, and this input excitotoxicity is believed to trigger neuropathic pain. However, the potential role of taurine in suppressing neuropathic pain has not been determined.There are a number of electrophysiological studies indicating that taurine exerts its actions by interacting with different ion channels, including Na~+ channels. However, currently few data may have been available on the action of taurine on Na~+ channels widely expressed in neural system, including DRG. This point may be neglected because of the preferential regard to the neuroinhibitory action of taurine by activating gamma-aminobutyric acid (GABA) or glycine receptors. Since there are no native glycine receptors in DRG neurons and DRG neurons do not respond to taurine. In experiment I, we examined whether taurine could exert some apparent effects on Na~+ channels in DRG neurons. Because voltage-sensitive Na~+ channels are critical determinants of membrane excitability and many changes in them are associated with traumatic nerve damages. We found that taurine inhibits both TTX-S and TTX-R Na~+ channels with a more potent effect on the former one. This study may provide a new mechanistic explanation for the taurine-modulated membrane stabilization involved in neural protection and a theoretical basis for the therapeutic application of this amino acid.On the other hand, our previous results showed that dietary taurine supplementprotected rats from the impairments of synaptic plasticity induced by postnatal leadexposure. However, little is known about the possible role of taurine in the presenceof fetal lead exposure. It is well documented that the induction, expression, andmaintenance of long-term potentiation (LTP), a principal experimental model used tostudy the role of synapses in learning and memory, are impaired in hippocampaldentate gyrus (DG) and CA1 regions of animals exposed to lead. Recently, severalclinical studies investigated the effects of low-level prenatal and perinatal leadexposure on intellectual development in children and found that mater-derived leadexposure would have a more powerful and lasting impact on neurobehavioraldevelopment of offspring than postnatal exposure. Actually, even very low level ofmaternal blood lead (10μg/dL) may induce intelligence quotient changes in the child.In the Experiment II, we investigate the protective role of taurine in differentdevelopmental periods and determined the developmental periods that are critical forproper protection from synaptic plasticity deficits in the rat pups with prenatal andperinatal lead exposure. Our data indicate that taurine can protect the adult rats fromsynaptic plasticity deficits following prenatal and perinatal lead exposure, and theprotective effects are critical for the prenatal and lactation periods of lead-exposedrats. In developing countries, the pollution of lead turns into a severe problem whichemphasizes the proper protection of taurine in the pregnant woman. This experimentsuggests that the time window and dosage of taurine supplement should be considered in the future community intervention.