PMID- 19779137
OWN - NLM
STAT- MEDLINE
DCOM- 20091209
LR  - 20220309
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 175
IP  - 4
DP  - 2009 Oct
TI  - Degenerating synaptic boutons in prion disease: microglia activation without 
      synaptic stripping.
PG  - 1610-21
LID - 10.2353/ajpath.2009.090372 [doi]
AB  - A growing body of evidence suggests that the loss of synapses is an early and 
      major component of a number of neurodegenerative diseases. Murine prion disease 
      offers a tractable preparation in which to study synaptic loss in a chronic 
      neurodegenerative disease and to explore the underlying mechanisms. We have 
      previously shown that synaptic loss in the hippocampus underpins the first 
      behavioral changes and that there is a selective loss of presynaptic elements. 
      The microglia have an activated morphology at this stage but they have an 
      anti-inflammatory phenotype. We reasoned that the microglia might be involved in 
      synaptic stripping, removing synapses undergoing a degenerative process, and that 
      this gives rise to the anti-inflammatory phenotype. Analysis of synaptic density 
      revealed a progressive loss from 12 weeks post disease initiation. The loss of 
      synapses was not associated with microglia processes; instead, we found that the 
      postsynaptic density of the dendritic spine was progressively wrapped around the 
      degenerating presynaptic element with loss of subcellular components. 
      Three-dimensional reconstructions of these structures from Dual Beam electron 
      microscopy support the conclusion that the synaptic loss in prion disease is a 
      neuron autonomous event facilitated without direct involvement of glial cells. 
      Previous studies described synapse engulfment by developing and injured neurons, 
      and we suggest that this mechanism may contribute to developmental and 
      pathological changes in synapse numbers.
FAU - Siskova, Zuzana
AU  - Siskova Z
AD  - CNS Inflammation Group, Basset Crescent East, School of Biological Sciences, 
      University of Southampton, Southampton SO16 7PX, UK. z.siskova@soton.ac.uk.
FAU - Page, Anton
AU  - Page A
FAU - O'Connor, Vincent
AU  - O'Connor V
FAU - Perry, Victor Hugh
AU  - Perry VH
LA  - eng
GR  - G0501636/MRC_/Medical Research Council/United Kingdom
GR  - G0501636./MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090924
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
SB  - IM
MH  - Animals
MH  - Dendritic Spines/pathology/ultrastructure
MH  - Disease Progression
MH  - Hippocampus/pathology/ultrastructure
MH  - Image Processing, Computer-Assisted
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*pathology/ultrastructure
MH  - Models, Biological
MH  - Presynaptic Terminals/*pathology/ultrastructure
MH  - Prion Diseases/*pathology
PMC - PMC2751557
EDAT- 2009/09/26 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/01
CRDT- 2009/09/26 06:00
PHST- 2009/09/26 06:00 [entrez]
PHST- 2009/09/26 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - S0002-9440(10)60672-4 [pii]
AID - 10.2353/ajpath.2009.090372 [doi]
PST - ppublish
SO  - Am J Pathol. 2009 Oct;175(4):1610-21. doi: 10.2353/ajpath.2009.090372. Epub 2009 
      Sep 24.