Characteristic Response of Striatal Astrocytes to Dopamine Depletion
Neural Regeneration Research(2019)
摘要
Astrocytes and astrocyte-related proteins play important roles in maintaining normal brain function,and also regulate pathological processes in brain diseases and injury.However,the role of astrocytes in the dopamine-depleted striatum remains unclear.A rat model of Parkinson’s disease was therefore established by injecting 10μL 6-hydroxydopamine(2.5μg/μL)into the right medial forebrain bundle.Immunohistochemical staining was used to detect the immunoreactivity of glial fibrillary acidic protein(GFAP),calcium-binding protein B(S100B),and signal transducer and activator of transcription 3(STAT3)in the striatum,and to investigate the co-expression of GFAP with S100B and STAT3.Western blot assay was used to measure the protein expression of GFAP,S100B,and STAT3 in the striatum.Results demonstrated that striatal GFAP-immunoreactive cells had an astrocytic appearance under normal conditions,but that dopamine depletion induced a reactive phenotype with obvious morphological changes.The normal striatum also contained S100B and STAT3 expression.S100B-immunoreactive cells were uniform in the striatum,with round bodies and sparse,thin processes.STAT3-immunoreactive cells presented round cell bodies with sparse processes,or were darkly stained with a large cell body.Dopamine deprivation induced by6-hydroxydopamine significantly enhanced the immunohistochemical positive reaction of S100B and STAT3.Normal striatal astrocytes expressed both S100B and STAT3.Striatal dopamine deprivation increased the number of GFAP/S100B and GFAP/STAT3 double-labeled cells,and increased the protein levels of GFAP,S100B,and STAT3.The present results suggest that morphological changes in astrocytes and changes in expression levels of astrocyte-related proteins are involved in the pathological process of striatal dopamine depletion.The study was approved by Animal Care and Use Committee of Sun Yat-sen University,China(Zhongshan Medical Ethics 2014 No.23)on September 22,2014.
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关键词
6-hydroxydopamine,astrocyte,dopamine depletion,dopaminergic neurons,Parkinson's disease,S100B,STAT3,striatum
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