The Study Of The Impaired Learning And Memory Induced By Developmental Lead Exposure And Its Pharmaceutical And Psycho-behavioural Intervention

Chronic developmental lead exposure is known to be associated with learningand memory and cognitive dysfunction in children. Synaptic plasticity such aslong-term potentiation (LTP) is believed to be the mechanism underling certain typeof learning and memory. The hippocampus-dependent spatial learning and memoryare correlated closely with hippocampal LTP, impairment of which often leads tomemory deficits. Previous studies have demonstrated that Pb impairs LTP of CA1 invitro and LTP of dentate gyrus in vivo. At present, chelation therapy is popular fortreating lead-induced neurotoxicity. But the common chelation agents have manyadverse effects and are incapable of alleviating lead-induceed neurotoxicity. It is veryimportant to explore medicine and intervention to rescue the impairment of learningand memory induced by lead. S-adenosyl-L-methionine (SAM) has beendemonstrated effective in reducing blood lead concentation and improving ALADactivity in humans and rats. But it is not clear if SAM is helpful to rescue theimpairment of learning and memory induced by lead. Enriched environment(EE) hasbeen adopted to interfere some brain damage such as very low birth weight andhypoxic-ischemic encephalopathy(HIE).Epidemiological studies showed that thechildren exposed to low lead from fortunate socioeconomic environments werecognitively intact while those in poor socioeconomic environments were cognitivelyimpaired. It is not very clear about the change of synaptic plasticity by EE treatmenton lead-exposed rats. In this thesis, the studies were carried out to investigate SAMand EE on the impairment of spatial learning and memory and LTP induced bydevelopmental lead exposure respectively. The results as follows:1.Rats drank 1500ppm lead acetate (PbAc) solution or distilled water throughout gestation and lactation. After weaning at postnatal day 22, one half of the control and lead-exposed male offspring were intraperitoneally injected 20 mg SAM/kg daily over a period of 20-22 days. Electrophysiological and Morris Water maze (MWM) test were performed at 44-54 days of age. The blood lead concentration and oxidative stress in liver, brain and hippocampus were also detected in the four groups as well. The result showed that the impaired learning ability induced by lead could be improved significantly by SAM. Furthermore, our results revealed that EPSP LTP and PS LTP impairments induced by lead were also ameliorated by SAM treatment. A significant recovery of blood lead, liver, brain glutathion (GSH) and malondialdehyde (MDA) level was clearly produced in lead-exposed rats after SAM treatment as well. This study showed that SAM is beneficial in the treatment of lead intoxication especially in the rescue of learning and memory impairment induced by lead and deserves more detailed research.2. Rats drank 1500ppm PbAc solution or distilled water throughout gestation and lactation. After weaning at postnatal day 21, one half of the control and lead-exposed male offspring were given the environmental enrichment treatment through all experiments until tested. Electrophysiological and Morris Water maze test were performed at 8 weeks of age. The result showed that the impaired learning ability induced by lead could be reversed by EE. Furthermore, our results revealed that EPSP LTP and PS LTP impairments induced by lead were also reversible by EE experience.