The effects of trehalose administration on autophagy enhancement in mice with conditional and progressive degeneration of medial spiny neurons

• Autorzy: Kreiner G. , Rafa-Zablocka K. , Baginska M. , Nalepa I.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: In neural cells, autophagy is proposed to serve as a surveillance mechanism which helps to clear protein aggregates, and loss of autophagy leads to neurodegeneration in mice. Our previous experiments, performed on genetically engineered mice with conditional and progressive neurodegeneration of medial spiny neurons (TIF-IAD1RCre mice) mimicking the typical progression of Huntington’s disease (HD), showed that the delayed onset of neurodegeneration observed in these mutants might be associated with temporary increased autophagy. The aim of current study was to evaluate a new strategy proposed recently for the anti-HD treatment, based on enhancing autophagy by administration of trehalose, a natural alpha-linked disaccharide. METHODS: Trehalose (2%) was dissolved in water and presented to the mice as a replacement for their water bottles for 1 or 2 months prior the experiments. The effects of trehalose were compared with groups receiving maltose (2%) as well as water (vehicle). The autophagy was determined by Western blot (WB) and immunohistochemistry (IHC) with use of anti-LC3B antibody. The animals were screened for their motor coordination by accelerated rotarod, and post-mortem for selected neurodegenerative markers by WB and IHC. RESULTS: Both control and mutant mice showed enhanced autophagy after trehalose administration as revealed by WB and IHC staining. Nevertheless, further analysis of quantitative assessment of several neurodegenerative markers by WB did not reveal any significant effects in attenuating the neurodegenerative process. There have been also no differences in behavioral phenotype. CONCLUSIONS: Our results provide additional evidence for stimulation of autophagy evoked by chronic administration of trehalose. However further study is needed, the enhancement of autophagy has not yet been proved to be neuroprotective in investigated model. Supported by 2011/03/B/NZ7/05949 grant financed by National Science Center (NCN).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S102

Twórcy

autor

Kreiner G.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Rafa-Zablocka K.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Baginska M.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Nalepa I.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland