Baicalein Inhibits Α-synuclein Oligomer Formation and Prevents Progression of Α-synuclein Accumulation in a Rotenone Mouse Model of Parkinson's Disease

Document Type

Article

Publication Date

2016

Keywords

PDParkinson disease, Parkinson disease, α-synα-synuclein, α-synuclein, SNsubstantia nigra, substantia nigra, LBsLewy bodies, Lewy bodies, PFAparaformaldehyde, paraformaldehyde, THtyrosine hydroxylase, tyrosine hydroxylase, PBSphosphate buffered saline, phosphate buffered saline, ChATcholine acetyltransferase, choline acetyltransferase, HPLChigh performance liquid chromatography, high performance liquid chromatography, DAdopamine, dopamine, DOPAC3, 4-dihydroxyphenylacetic acid, 3, 4-dihydroxyphenylacetic acid, HVAhomovanillic acid, homovanillic acid, EDTAethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid, SDS-PAGEsodium dodecyl sulfate-polyacrylamide gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, GAPDHglyceraldehyde-3-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, TEMtransmission election microscopy, transmission election microscopy, DMSOdimethylsulfoxide, dimethylsulfoxide, SDstandard deviation, standard deviation, ENSenteric nervous system, enteric nervous system, IMLintermediolateralnucleus, intermediolateralnucleus, UPSubiquitin-proteasome system, ubiquitin-proteasome system, ALPautophagy-lysosome pathway, autophagy-lysosome pathway, GABAAγ-aminobutyric acid, γ-aminobutyric acid, Baicalein, Flavonoid, Parkinson's disease, Neurodegenerative disease, α-Synuclein, Rotenone

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.bbadis.2016.07.008

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5 mg/kg, 12 weeks). Baicalein (100 mg/kg) was intraperitoneally injected from 7 week to 12 week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.

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Citation / Publisher Attribution

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, v. 1862, issue 10, p. 1883-1890

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