| ObjectiveThe heavy metal lead is a well - known environmental toxicant, whose neurotoxicity is an important public health concern because lead is very prevalent and it can cause apparently irreversible damage to the nervous system, particularly to the young. Due to incompletely developed blood brain barrier, children who were exposure to lead as low as 100 ug/L (blood lead level) have shown significant deficits of cognitive functions and significant delays in behavioral development. Consistent with these observations, studies on animal models have indicated an impairment of learning and memory following low level lead exposure, which results in relevant blood concentration.The deleterious effects of lead exposure on cognitive abilities have evoked a number of experimental studies to characterize the neurotoxicological effects of lead. The pb2+ can mimic Ca2+ in a number of calcium mediated cellular processes, by which lead exhibits several actions that could alter nervous system function. For example, lead can decrease depolarization evoked neurotransmitter release in neuromuscular junction and synaptosome, inhibit glutamatergic neuro-transmission at the NMDAR complex, interfere with the activation of protein ki-nase C. however, the mechanism underlying the lead induced learning impairments have not been defined.CaMK II is highly abundant in the brain and a major constituent of the postsynaptic density (PSD). It assembles into hetero - oligomeric complexes.Calcium influx through NMDA receptors results in activation of CaMK fl and au-tophosphorylation of Thr286. This autophosphorylation allows the kinase to be active even in the absence of calcium. In addition, Thr286 phosphorylation promotes association with the postsynaptic density by binding to the NMDA receptor. Hence, a transient increase in calcium can dramatically change the activity and the localization of this kinase. Importantly, both the induction of long term potentiation and behavioral training are known to trigger autophosphorylation of a CaMK II at Thr286, suggesting that this mechanism is critical for synaptic and behavioral plasticity.The first direct evidence that the MAPK cascade is involved in synaptic plasticity came from English and Sweatt in 1996. the authors first showed that ERK2 is activated in rat hippocampal area CA1 following NMDA receptor stimulation in the hippocampus. In a subsequent paper, the authors showed that ERK activation is required for the induction of stable CA1 long term LTP, making use of an inhibitor of ERK activation, PD98059. In many additional studies show other LTP inducing stimulation protocols and spatial learning have also been shown to be ERK dependent.Though many have proved that Extracellar signal regulated/ mitogen activated protein kinase (ERK/MAPK) and CaMK II play important roles in learning and memory, effects of lead on ERK2 and CaMK II is still a mystery. Our aim is to find the change of these two kinases under this condition, and further to discovery the mystery of lead poison.Materials and MethodsThe protocols for chronic exposure to lead are as follow; Wistar rats were purchased from animal Department of China medical University (CMU) and were individually housed in plastic cages. Rats were randomly and equally divided into four groups. Female rats were mated with male of same strain. On postnatal day 1, the dam began exposed to lead at 0, 0.022% , 0.067% , and 0. 200% in their drinking water. In order to insure equal access for each pup to the dam's milk, litters were culled to 10 pups. After weaning at postnatal 21 d,the pups were directly provided lead acetate in drinking water. Food and water were provided ad libitum. Until 80 d, the pups were trained in a spatial learning task using a water maze paradigm, and then determined LTP alternately and hippocampus was got. The activities of ERK2 and CaMK II were determined with Western blots; the mRNA of CaMK II was determined with RT - PCR.The protocols for acute exposure to lead are as follow: For acute lead expose in...
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