BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:Special LMNN SEMINAR // 2 talks\, 20 min. each
DTSTART:20170621T091500
DTEND:20170621T101500
DTSTAMP:20260510T183458Z
UID:95b3209bd78b837854c3b7808851641ec8dfc5fa0f61d4d3ce78d773
CATEGORIES:Conferences - Seminars
DESCRIPTION:Manuel Buttini\, Neuropathology Core\, Luxembourg Centre for S
 ystems Biomedicine\, University of Luxembourg\, Luxembourg\n1. "Inclusion-
 Independent Neurodegeneration in a Mouse Synuclein-Spreading Model of PD: 
 an Active Role for Microglia?"\n \nA key process in many types of chronic
  neurodegeneration is the transneuronal spreading of aggregation-prone pro
 teins\, such as a-synuclein. Alpha-synuclein is a presynaptic protein that
  is implicated in the pathogenesis of Parkinson’s disease (PD) and other
  synucleopathies\, where it forms\, upon intracellular aggregation\, patho
 logical inclusions. Notably\, transneuronal spreading of a-synuclein patho
 logy appears as a basic mechanism of PD progression. Whether transneuronal
  spreading of a-synuclein particles\, aggregation formation\, or other mec
 hanisms are directly causing neurodegeneration is unclear. Here\, we use a
  model of spreading/aggregation of a-synuclein induced by intracerebral in
 jection of preformed fibrils into mouse brain to address this question. We
  observed significant neurodegeneration and microgliosis in brain regions 
 with\, but also\, just as importantly as without\, a-synuclein inclusions\
 , and these regions were either close or distant from the fibril injection
  site. We also observed that the level of microgliosis in injured brain re
 gions\nwas unusually strong\, and didn’t correlate with neurodegeneratio
 n. In gene epxression profiling studies\, we couldn’t detect any changes
  in the expression of usual proinflammatory cytokines and chemokines that 
 a typically enhanced during neuroinflammation\, but instead observed that 
 modulations of factors such as Toll-like-rector 2\, TREM2\, NAPDH oxidase 
 2\, and prostaglandin synthesis components indicated an unique microglial 
 activation profile that could promote neurodegeneration in susceptible bra
 in regions. Our observations indicate that inclusion formation may not be 
 the only driver of PD-like neurodegeneration\, but that other factors\, su
 ch as diffusible a-synuclein species\, or unique microglia activity\, play
  a role in the process. Our findings uncover novel features of a-synuclein
  induced pathologies\, and point to the necessity of a broader view of the
  process of “prion-like spreading” of that protein.  \n\n \n"Early 
 Gene Expression Changes in Dopaminergic Neurons Precede PD-Related Neurode
 generation in Synuclein-Based Mouse Models of PD: A Possible New Path to B
 iomarker Discovery"\n \nUnderstanding early\, and therefore often subtle\
 , disease processes in Parkinson’s disease (PD) is essential for the ide
 ntification of biomarkers and the development of disease modifying cures. 
 But in patients\, and in many PD animal models\, measurable neurological s
 ymptoms occur only at disease stages in which neuronal injury and loss has
  typically already progressed beyond repair. To investigate if measures of
  gehn expression profile changes help detect early disease processes\, and
  thus open the way to biomarker\, we investigated those profiles in the br
 ain of synuclein-based genetic and induced PD models. - We investigated ge
 ne expression profiles in brain extracts of these models\, and compared th
 em with behavioural and neuropathological measures. By analyzing the ventr
 al midbrain at different ages\, or time-points of disease progression\, we
  drew out changes in gene expression patterns that coincided\, and often p
 receded\, with subtle\, early motor disturbances\, and were\, for the most
  part\, independent of neuropathological changes such as the presence of s
 ynuclein aggregates and overt neurodegeneration and gliosis. Thus\, by app
 lying profiling\, or “systems” approaches to rodent models of PD\, we 
 identified interesting disease related changes that pave the way for a bet
 ter understanding of the earliest disease processes.\n\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
END:VEVENT
END:VCALENDAR