| IntroductionNitric oxide ( NO) is a gaseous chemical messenger which plays the role of a universal modulator of various physiological functions of animals including the nervous system, i. e. , interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, release of neurotransmitters. The possible role of NO is considered in some basic diseases of the central nervous system which are associated with the neurotoxic effect of glutamate. NO is believed to be a key pathophysiological factor of these diseases. The production of NO in the brain cortex of rats was found to significantly increase during convulsions of various origin. Nitric oxide synthases ( NOSs) , including nNOS,iNOS,eNOS, the enzymes are responsible for synthesis of NO . Presynaptic membrane of the neuron release glutamate, the excitatory neurotans-mitter activates the NMDA receptor so that produes prototypic NOS in the posts-ynaptic membrane.Mitogen - activated protein kinase ( MAPKs) , also known as extracellular signal - regulated protein kinases ( p44/ERKl and p42/ERK2 ) , play a important role in signal transduction in all eukaryotic cells. MAPKs represent the convergence point for many signaling pathways and they, in turn, modulate a variety of cellular events.The glial cell line -derived neurotrophic factor (GDNF) is first characterized for its trophic activity on dopaminergic neurons. Recent data suggested that GDNF could modulate the neuronal death induced by animal model of ischemiainjury etc. Neuroprotection mediated by GDNF: involvement of a reduction of NMDA - induced calcium influx by the mitogen - activated protein kinase pathway.The N - methyl - D - aspartate ( NMDA) receptor is a subtype of the ionic glutamate channel receptor including NR1, NR2(NR2A, NR2B and NR2C)and NR3 subunits that plays a pivotal role in synaptic mechanisms of learning and memory. NMDA receptor not only regulate Na + , K+ ionic channel but also control Ca2+ channel. When they are activated, Na+~K+ ionic flow acoss the cell membrane will occur. Ca + is considered as a second messenger,which may directly or indirectly influnce the NMDA receptor,so that improve its transmission efficacy. But highly active NMDA receptor channels are formed only when the NR2A(el) and NRl(gl) subunits are expressed together.Glutamic acid (Glutamate) is one kind of central excitatory neurotransmit-ter,its target cell is neurons that have metabolic glutamate receptor(mGluR) N NMDA receptor and non - NMDA receptor. It play a important role in tne excitatory synaptic transmission, learning and memory, synaptic plasticity, but excessive excitation of brain neurons by the excitatory neurotransmitter, glutamate, induces a cascade of events leading to increased intracellular Ca + and neuronal degeneratsion and death. One of main questions for discussion of hippocampus CA1 selectively injuried by in the neuronal degeneratsive field is in the study of aging and Alzheimer's disease (AD) , however, the latter is directly associated with injuries. Such degeneratsive diseases have one of notable characteristics that is dysfunction of learning and memory in the central nervous system. Various neurotoxins have been used to achieve this in animal models. So we use excessive glutamic acid to build AD model rats in order that test the hypothesis that effects of wide brand noise on the expressions of NOS1, ERK, GDNF, NR1 and NR2A(NMDA receptor protein) subunits levels as well as ABR thresholds in the different area of brain of AD rats are associated with each other in molecular level mechanisms.MaterialsNMDAR1 ( ζ1),MDAR2A( el)goat polyclonal IgG(200μg/ml), GDNF rats polyclonal IgG(200μLg/ml) was purchased from santa cruze biotechnology, phosphorylated-P44/42MAPK ( Thr202/Tyr204 ) monoclonal IgG (ERK) was purchased from New England Biolabs. Inc; L - Glutamate was purchased from Sigma; TRIZOL Lots was purchased from Gibco/BRL,USA; ECL fluorescence lots was purchased from Pamacia, USA.Methods1. Animal model pr...
|
PDF Full Text Request