Objective To observe the influence of rotenone on the distribution of α-synuclein (ASN) in rat model of Parkinson's disease (PD). Methods Wistar rats were randomly divided into two groups and received 2 mg/kg ro...Objective To observe the influence of rotenone on the distribution of α-synuclein (ASN) in rat model of Parkinson's disease (PD). Methods Wistar rats were randomly divided into two groups and received 2 mg/kg rotenone (s.c.) or sunflower oil (as control group) for about 4 weeks. The hippocampus, substantia nigra and striatum of brain were observed. Hematoxylin and eosin stain were used to observe the Lewy body like inclusion. The expression of tyrosine hydroxylase (TH) or ASN protein was determined by anti-TH or anti-α-synuclein immunohistochemistry, respectively. Results In control rats, ASN protein distributed widely in brain, especially in hippocampus, cortex and striatum. Rotenone obviously increased TH positive neurons and fibers loss in substantia nigra and striatum (P 〈 0.05). In rotenone treated rats, ASN positive cells increased in global brain but not distributed in an even manner. In substantia nigra, ASN positive stuff was found aggregate in both cytoplasm and nucleus, and some formed spherical inclusion; in striatum, ASN positive neurites end aggregated and agglomerated around neurons; and in hippocampus, few dot-like ASN were aggregated in cell body, and no notable change was found in nucleus. Conclusion In rotenone administrated PD rats, ASN protein aggregated in several brain regions but most obviously in striatum and substantia nigra, and the distribution region of ASN was changed from peri-synapse to the cytoplasm and nucleus of dopaminergic neuron.展开更多
Objective Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson’s disease.The main component of LB is aggregatedα-synuclein,present in the substantia nigra where iron accumulation also occ...Objective Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson’s disease.The main component of LB is aggregatedα-synuclein,present in the substantia nigra where iron accumulation also occurs.The present study was aimed to study the relationship between iron andα-synuclein aggregation.Methods SK-N-SH cells were treated with different concentrations of ferric iron for 24 h or 48 h.MTT assay was conducted to determine the cell viability. Thioflavine S staining was used to detectα-synuclein aggregation.Results With the increase of iron concentration,the cell viability decreased significantly.At the concentrations of 5 mmol/L and 10 mmol/L,iron inducedα-synuclein aggregation more severely than at the concentration of 1 mmol/L.Besides,48-h treatment-induced aggregation was more severe than that induced by 24-h treatment,at the corresponding iron concentrations.Conclusion Ferric iron can induceα-synuclein aggregation,which is toxic to the cells,in a dose-and time-dependent way.展开更多
基金supported by the National Nature Science Foundation of China(No.30570627).
文摘Objective To observe the influence of rotenone on the distribution of α-synuclein (ASN) in rat model of Parkinson's disease (PD). Methods Wistar rats were randomly divided into two groups and received 2 mg/kg rotenone (s.c.) or sunflower oil (as control group) for about 4 weeks. The hippocampus, substantia nigra and striatum of brain were observed. Hematoxylin and eosin stain were used to observe the Lewy body like inclusion. The expression of tyrosine hydroxylase (TH) or ASN protein was determined by anti-TH or anti-α-synuclein immunohistochemistry, respectively. Results In control rats, ASN protein distributed widely in brain, especially in hippocampus, cortex and striatum. Rotenone obviously increased TH positive neurons and fibers loss in substantia nigra and striatum (P 〈 0.05). In rotenone treated rats, ASN positive cells increased in global brain but not distributed in an even manner. In substantia nigra, ASN positive stuff was found aggregate in both cytoplasm and nucleus, and some formed spherical inclusion; in striatum, ASN positive neurites end aggregated and agglomerated around neurons; and in hippocampus, few dot-like ASN were aggregated in cell body, and no notable change was found in nucleus. Conclusion In rotenone administrated PD rats, ASN protein aggregated in several brain regions but most obviously in striatum and substantia nigra, and the distribution region of ASN was changed from peri-synapse to the cytoplasm and nucleus of dopaminergic neuron.
基金supported by the grants from the National Basic Research Development Program of China(No.2006CB500704)the National Natural Science Foundation of China(No.30930036,30870858)the Natural Science Fund for Distinguished Young Scholars of Shandong Province,China(No.JQ200807)
文摘Objective Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson’s disease.The main component of LB is aggregatedα-synuclein,present in the substantia nigra where iron accumulation also occurs.The present study was aimed to study the relationship between iron andα-synuclein aggregation.Methods SK-N-SH cells were treated with different concentrations of ferric iron for 24 h or 48 h.MTT assay was conducted to determine the cell viability. Thioflavine S staining was used to detectα-synuclein aggregation.Results With the increase of iron concentration,the cell viability decreased significantly.At the concentrations of 5 mmol/L and 10 mmol/L,iron inducedα-synuclein aggregation more severely than at the concentration of 1 mmol/L.Besides,48-h treatment-induced aggregation was more severe than that induced by 24-h treatment,at the corresponding iron concentrations.Conclusion Ferric iron can induceα-synuclein aggregation,which is toxic to the cells,in a dose-and time-dependent way.