Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydroxycholesterol (cerebrosterol)/cholesterol ratio when compared to controls. In this study, effects of amyloid beta peptides and of racemic 24-hydroxycholesterol were evaluated in vitro on undepleted or cholesterol-depleted hippocampal synaptosomes of young and old rats via a high-affinity choline transport and membrane anisotropy measurements. Depletion of membrane cholesterol decreased the transport of [3H]choline, increased the specific binding of [3H]hemicholinium-3 and decreased membrane anisotropy. However, less alterations were found in old when compared to young brains. 500 nM nonaggregated peptides were ineffective but aggregated fragment 1-42 evoked marked drops in the transport and anisotropy values on depleted synaptosomes. 50 microM 24-hydroxycholesterol inhibited choline transport on depleted synaptosomes but it did not influence membrane anisotropy. Peptides eliminated the actions of oxysterol on choline carriers in young but not in old rats. On the other hand, oxysterol eliminated the effects of peptides on membrane anisotropy. Our study suggests a possible role of membrane cholesterol in the regulation of choline carriers and supports data reporting a protective role of membrane cholesterol against toxic effects of amyloid beta peptides. Moreover, via Raman spectroscopy we demonstrate for the first time that peptides form a complex with 24-hydroxycholesterol.

• MeSH
• amyloidní beta-protein chemie   toxicita   MeSH
• anizotropie MeSH
• cholinergní látky farmakologie   MeSH
• difenylhexatrien MeSH
• financování organizované MeSH
• fluidita membrány účinky léků   MeSH
• fluorescenční barviva MeSH
• hemicholinium 3 farmakologie   MeSH
• hipokampus metabolismus   účinky léků   MeSH
• hydroxycholesteroly chemie   toxicita   MeSH
• interpretace statistických dat MeSH
• krysa rodu rattus MeSH
• membránové transportní proteiny metabolismus   MeSH
• membrány metabolismus   účinky léků   MeSH
• potkani Wistar MeSH
• proteiny přenášející neurotransmitery metabolismus   MeSH
• Ramanova spektroskopie MeSH
• stárnutí fyziologie   MeSH
• synaptozomy metabolismus   účinky léků   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH