Dissertation > Medicine, health > Neurology and psychiatry > Psychiatry > Mental disorders of toxic > Alcohol disorder

The Changes of Rat Learning Capacity and Memory and the Mechanisms of Synaptic Damage after Chronic Alcohol Drinking

Author YinMeiFang
Tutor CongBin
School Hebei Medical University
Course Forensic
Keywords Drinking hippocampus water maze Syn PSD95 GAP43 synaptic plasticity
CLC R749.62
Type Master's thesis
Year 2014
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Objective: At present, more and more teenagers are prematurely exposedto alcoholic beverage and even drink heavily. Excessive drinking not onlyresult in serious social harm, such as traffic accidents and publidc disorderafter drinking, but also cause harm to human health, including a seriousimpairment of nerval, circulatory and digestive system. As one of neurotropicsubstances, damage of the nervous system induced by alcohol is obvious.Many studies on alcohol toxicity of nervous system are concentrated on thesynaptic plasticity. The hippocampal synaptic plasticity plays a role onlearning capacity and memory related to environment. The impairment ofhippocampal neurons after chronic drinking will lead to disorder of cognitive,learning and memory capacity.The neurobiological basis of learning and memory function isthe synaptic plasticity.Synaptophysin (Syn) is a index widely used to observesynaptic plasticity. It is a calcium binding protein closely related to thesynaptic structure and function. It is mainly transported to the axon terminalsof neurons after synthesis in the endoplasmic reticulum, specificallydistributed in the presynaptic vesicle membrane, and regulatedcalcium-dependent neurotransmitter release. Growth associated protein43(GAP43) is a kind of presynaptic membrane protein, is involved in cell growthand synaptic formation. GAP43can change cell morphology through mediateaxon elongation. Under normal circumstances, was expressed at low levels. Inneuronal development and injury cases, GAP43expression elevated.Postsynaptic density (PSD95), one of cytoskeletal proteins, is a maincomponent of postsynaptic density, and has a high degree of stability. Itsdifferent domain can form stable lattice, so that different proteins enter intothe lattice after the stimulation, which mediates the interactions between the proteins and the proteins redistribution and regulated response to neuronalsignals. These three proteins play an important role in synaptic plasticity.Caspases3protease called death protease, is the key enzyme in the process ofcells apoptosis. Once activated, apoptosis is inevitable. Peroxynitrite(peroxynitrite, ONOO-) can be used as a strong oxidant or protein nitrationagent, cause structure modification or dysfunction of many importantbiological macromolecular. The protein tyrosine residues can benitrificationby ONOO-, forming3-nitrotyrosine (3-nitrotyrosine,3-NT). Therefore,3-NTis often used as a biomarkers in vivo production of ONOO-. Caspases3andONOO-are involved in apoptosis and necrosis of neuronal cells.Up to now, whether the long-term drinking changes the structure ofsynaptic plasticity and effects of spatial learning and memory ability byinfluencing the expression of the protein in the hippocampus of rats, is notvery clear.This study was designed to observe the effects of chronic alcoholdrinking on the spatial memory ability of rats, test the change of hippocampussynapse associated protein expression. The results should be helpful toanalysis of synaptic structure change in hippocampal region of rats, andelucidate the molecular mechanism of spatial memory impairment.Methods:Sprague-Dawley(SD) rats were randomly divided into following groups:control group(n=10)and alcohol group(n=25). Rats were treated with wine ofBeijing Hongxing (56%v/v) to prepare model. Before modeling, rats weregiven normal feeding for a week. Alcohol group was supplied with5%alcoholfor2weeks. Then gradient increasing concentrations of alcohol of10%and15%were respectively given for2weeks. Then20%alcohol were given as theonly source of water, until the end of the10thmonth. Water instead of alcoholwas given to control group. We recorded the weight. Use Morris water maze(MWM), we tested function of learning and memory ability in rats. Themorphologic changes of hippocampus neuron cells were observed by thioninstaining. Expression of Syn、PSD、GAP43、Caspases3and3-NT protein were detected by immunohistochemical staining and western bloting.Results:1Changes of the basic condition and weight of rats: After chronicdrinking, the rats appeared anepithymia, torpidity to stimulus, weight-decreaseand dry fur. The body weight of alcohol group significantly decreasedcompared with the normal group (P <0.01).2Changes in behavior: the space exploration achievements andnavigation experiments of chronic drinking rats were decreased comparedwith the normal group (P <0.01).3Thionin staining. In chronic alcohol drinking group, the hippocampalnerve cells in CA1region decreased with disorder of cell-scatterring, edemaand degeneration necrosis.4The expression of protein in hippocampal CA1region: Thehippocampal CA1neurons of both control group and the chronic alcoholdrinking group had positive expression of PSD95and Syn protein in brownstainning. In the chronic alcohol drinking rats, staining of PSD95proteinshowed weak, while Syn strong. Results of Western Blot implicated thatchronic alcohol drinking rat hippocampus PSD95protein expressiondecreased, and Syn、GAP43、Caspases3、3-NT protein increased, comparedwith the normal group (P <0.001).Conclusions:①The chronic drinking impairment the learning and memory of rats.②The chronic drinking can induced increase the expression of ONOO-andCaspases3, leading to apoptosis and necrosis of hippocampal neurons cell.③The long-term drinking reduced the expression of PSD95in postsynapticmembrane, affect of postsynaptic plasticity. The presynaptic membraneprotein of Syn、GAP43、Caspases3、3-NT expression increased, considered asa mechanism of compensatory synaptic remodeling after neuronal cell injury.

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