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Immunohistochemical Localization Of Glial Cell Line-deriveded Neurotrophic Factor (GDNF) And Its Receptor Complex (GFRα-1,Ret) In The Rat Brain With Unilateral Fimbria-formix Transection

Posted on:2003-09-15Degree:MasterType:Thesis
Country:ChinaCandidate:L K HuFull Text:PDF
GTID:2144360092996183Subject:Neurology
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IntroductionGlial cell line - derived neurotrophic factor( GDNF) is a neurotro-phic factor that influences the survival and function of several neuronal populations in the central (CNS) and peripheral nervous systems. GD-NF is a distant member of the transforming growth factor ?p family, originally isolated by virtue of its ability to induce dopamine uptake and cell survival in cultures of embryonic ventral midbrain dopaminer-gic neurons, and more recently it has been shown to be a potent neu-rotrophic factor for motorneurons. The actions of GDNF are mediated by a multicomponent receptor complex of the tyrosine kinase product of c - ret and the ligand - binding protion GDNF receptor alpha (GFRa -1 ). Investigations are currently focused on the action of GDNF in the cholinergic system of the basal forebrain because disturbances to this system may be involved in age - related neuropathologies such as Alzheimer ' s disease. The basal forebrain projection from the medial septum (MS) and diagonal band(DB) of Broca to the hippocampus provides a best ?characterized cholinergic pathway for the study of the role of GDNF in the animal CNS. Some observations obtained with this experimental system indicated that lesions of septohippocampal path-way reduced the septal and hippocampal ChAT activity.To investigate the possible effects of GDNF on the cholinergic system in the basal forebrain of rats, we examined the expression of GDNF and its receptors ( GFRa - 1 Ret) in the brains of rats with u-nilateral lesions of the fimbria by immunohischemistryMaterials and methodsMaterialsAntibodies: anti - GDNF,anti - Ret ,anti - GFRa - 1 were ob-tained from Santa Cruze technology company.Methods;A total of 10 male Wistar rats ( 3 - 5 months, 250 - 300g in weight) were used. They were kept on a normal day and night cycle , individually housed and were given free access to food and water.The animals were subdivided into two groups, one normal and one operated group, each group consisting of 5 rats. Unilateral partial lesion of the septohippocampal pathway was produced on the left side of the operated groups, as described by He yunshao . After two weeks, all rats were killed and the brain was removed, immersed in 4% paraformaldehyde ( PH7.4 ) for 24 hours, then were embedded by par-affin at 4 and cut into 5 - μm thick sections.Immunohistochemical procedures were adopted from the descrip-tion of Matsuo. All primary antibodies were diluted (1:50) .ResultsGDNF and its receptors ( GFRa - 1 ,Ret) were expressed in the neurons in hippocampus and cerebral cortexs of all rats. The positive immunocreations were located in the cytoplasm of neurons . The inten-sities of staining declined from the normal rats to the model rats, butthe changes of intensities had not statistical significance.DiscussionAlzheimers disease (AD) is the most common neurodegenerative disease happened in the old people and is the major reason for the de-mentia , with the character of disorders in memory, cognitive functions and behaviors. The etiologcal and etiopathogenesis of AD remains un-clear. " The loss of cholinergic neurons of the basal forebrain" are be-lieved to be involved in the pathogenesis of AD. The cholinergic neu-rons of nbM play an important role in the functional process of learning and memory. Impaired memory is a cardinal symptom in the diagnosis of AD. A morphological correlation of the cholinergic neurons in the basal forebrain and a loss of choline acetyltransferase in the cortex and hippocampus.The basal forebrain projection from the medial septum ( MS) and diagnosis band ( DB) of Broca to the hippocampus provides a best -characterized cholinergic pathway for the study of the role of the GDNF in the animal CNS. Some observations obtain with this experimental system indicated that lesions of septohippocampal pathway reduce the septal and hippocampal ChAT activity.In our study, we found the similar expressions of GDNF and its receptors ( GFRa -1, Ret) in hippocampus and cerebral cortexs of all...
Keywords/Search Tags:GDNF, GFRa - 1, Ret, molel rats with unilateral, fimbria - formix transection, immunohistochemis-try
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