Modulation of SIRT1 expression in different neurodegenerative models and human pathologies

Neuroscience. 2008 May 3. [Epub ahead of print]

Pallàs M, Pizarro JG, Gutierrez-Cuesta J, Crespo-Biel N, Alvira D, Tajes M, Yeste-Velasco M, Folch J, Canudas AM, Sureda FX, Ferrer I, Camins A.

Unitat de Farmacologia i Farmacognòsia, Facultat de Farmacia i Institut de Biomedicina (IBUB), Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028 Barcelona, Spain; Ciberned, Centro de Investigación Biomédica en Red de enfermedades Neurodegeneratias, Instituto de Salud Carlos III, Spain.

We examined the expression of SIRT1 in several experimental paradigms of human pathologies. We used a neuroblastoma cell line (B65), neuronal primary cultures (hippocampus and cerebellar granule cells) and in vivo approaches in rat and senescence murine models (SAM). Cell cultures and rats were treated with several well-know neurotoxins, i.e. rotenone, MPP(+), kainate and 3-nitropropionic acid. Subsequently, SIRT1 expression was compared in these different paradigms of neurotoxicity. The pattern of expression of SIRT1 in proliferating cell cultures (B65) was different to that in quiescent cell cultures. In the murine model of senescence (senescence-accelerated mice prone, SAMP8), SIRT1 expression progressively decreased, while in the control strain (senescence-accelerated mice resistant, SAMR1) it increased. Finally, we studied human samples of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Huntington's diseases (HD). SIRT1 expression decreased dramatically in HD, but there were no significant changes in Parkinson-related illnesses. In conclusion, SIRT1 expression may be a good sensor of toxic neuronal processes.

PMID: 18538940 [PubMed - as supplied by publisher]