Effect Of Aluminum Exposure On LTP And Glu And NMDAR In Hippocampus Of Pups During Pregnancy And Lactation Matrix

PrefaceAluminium is one of the most redundant elements in the crust of the earth.Athough it is not highly noxious, but too much of it in our body can cause toxicity.There are many investigations and researches show that aluminium is most likely causeneuron impairment and decrease mentality and recognization. It is confirmed by animalexperiments that exposure of aluminium can cause rats dementia, which is not onlyappearances behavioral disturbance but also it's morph changes are most like AD.Hippocampus is the key brain region of study and memory, Long-TermPotentiation is synaptic transmission's continuity enhancing of the NMDA receptorsdepended. It is received study model of study and memory's function of brain at thesynapse level. It's induction and maintenance is depended on the multiple fore-synapticand post-synaptic. Consequently, studying the effect of aluminium on Long-TermPotentiation and approaching it's possible mechanisms can elucidate the mechanisms ofaluminium on study and memory.The research indicated that the pregnant and lactational stage is the importantstage for the filial brain growth and development. Effect of aluminum exposure at thisstage on the filial brain is a topic worthy of being studied thoroughly. Therefore, wemade the parent rats exposed to aluminum and took their pups as the subjectsinvestigated to study the effect of aluminum exposure on the formation, maintain ofLTP, and tried to elucidate the mechanism of aluminum impairing to LTP.Material and Methods 1. Animal and Treatment30 female Wistar rats aged 4 weeks and weighing about 180g were randomlydivided into three groups of 10 animals. Animals from the control group receiveddistilled water ad libitum as unique source of liquid. Animals from the experimentalgroup received a aluminium chloride solution (0.2% and 0.4%) ad libitum, as uniqueliquid source, female rats were administered aluminum chloride from the first day ofpregnancy to the ending of lactation. All pups changed to drink distilled water andbelonged to the group of its mother. When weighing about 200 g, pups were killed forexperiment.2. Methods(1) Ethology detectionEthology detection was detected by jumping stand experiment.(2) LTP recordThe technique of extracellular electrophysiological was used torecord the effect ofaluminium on long-term potentiation (LTP) in hippocampal CA1 area.(3) Aluminium concentration analysisAtomic absorption spectrophotomery(AAS) was used to detect the content ofAluminium in blood and brain.(4) Glutamate-immunoreactive neurons in hippocampusGlutamate-immunoreactive neurons in hippocampus were stained byimmunocytochemical method. The stucture,numbers and staining intensities of theseneurons were observed by microscope.(5) The changes in protein expression of NMDA receptor subunit NR1,NR2a andNR2b in hippocampus: western blot method.Results1. Aluminium concentration in blood and brainThe blood aluminium concentration in the rats of aluminium exposed groups were much higher than those of control groups. And there were significant changes in lowand high aluminium exposed groups. The same changes were there in brain aluminiumconcentration except the significant changes in low and high aluminium exposedgroups.2. Ethology detectionThe learning and memory were significant decreased in in the rats of aluminiumexposed groups. The latency period was significant longer than the control group,andthe error times was significant increased than the control group.3. LTP recordThe population spike(PS) in hippocampal CA1 was depressed in the rats ofAluminium exposed groups. And the higher dose the aluminium exposed the mucherdepressed.4. The numbers and staining intensities of glutamate-immunoreactiveneurons in hippocampusThe glutamate-immunopositive neurons in hippocampal CA1 area of pups incontrol group assume circular shape, regularly arranged with dark staining and theboundary is clear. But the arrangement of neurons in the low and high aluminumtreated groups is sparse, and the boundary is not clear with slight staining. Theglutamate-immunopositive neurons in hippocampal CA3 area are round, regularlyarranged with clear boundary and full of spinous puffs with dark staining. Thearrangement of neurons in aluminum exposed groups of low and high level is sparseand loose, unclear boundary and slightly stained.The average optical density of glutamate-immunopositive neurons in pupsexposed to aluminum of different concentration is significantly lower than that of thecontrol group in a dose-dependent manner. The more aluminum applied to animals, theless area of glutamate-immunopositive neurons in CA1 and CA3 area there is.5. The expression level of NMDA receptor subunit NR1,NR2a and NR2b in hippocampusNote the decrease in NR1 expression in the hippocampus of aluminum treatedgroups compared to control group(P＜0.05). NR2A expression in the hippocampus ofevery groups have no remarkable change. The NR2B expression in hippocampal wasdepressed in the rats of aluminium exposed groups, and the higher dose the aluminiumexposed, the mucher depressed.Conclusions1. Chronic aluminum exposure during pregnant and lactational stage can damagethe function of learning and memory of pups.2. Chronic aluminum exposure during pregnant and lactational stage has aninhibitory effect on the formation of LTP in CA1 area of pups.3. The aluminum-induced impairments to learning and memory may be due to itsinhibitory effects on the glutamate-immunopositive neurons in Hippocampus.4. Chronic aluminum exposure during pregnant and lactational stage can cause theproportion of NMDAR subunits to change, and the expression of NR1and NR2Bdepressed.