PMID- 22031903
OWN - NLM
STAT- MEDLINE
DCOM- 20111219
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 31
IP  - 43
DP  - 2011 Oct 26
TI  - The role of attenuated astrocyte activation in infantile neuronal ceroid 
      lipofuscinosis.
PG  - 15575-85
LID - 10.1523/JNEUROSCI.3579-11.2011 [doi]
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative 
      disorder affecting the CNS during infancy. INCL is caused by mutations in the 
      CLN1 gene that lead to a deficiency in the lysosomal hydrolase, palmitoyl protein 
      thioesterase 1 (PPT1). A murine model of INCL, the PPT1-deficient (PPT1(-/-)) 
      mouse, is an accurate phenocopy of the human disease. The first pathological 
      change observed in the PPT1(-/-) brain is regional areas of glial fibrillary 
      acidic protein (GFAP) upregulation, which predicts future areas of 
      neurodegeneration. We hypothesized that preventing GFAP and vimentin upregulation 
      in reactive astrocytes will alter the CNS disease. To test this hypothesis, we 
      generated mice simultaneously carrying null mutations in the GFAP, Vimentin, and 
      PPT1 genes (GFAP(-/-)Vimentin(-/-)PPT1(-/-)). Although the clinical and 
      pathological features of the GFAP(-/-)Vimentin(-/-)PPT1(-/-) mice are similar to 
      INCL, the disease appears earlier and progresses more rapidly. One mechanism 
      underlying this accelerated phenotype is a profound neuroinflammatory response 
      within the CNS. Thus, our data identify a protective role for intermediate 
      filament upregulation during astrocyte activation in INCL, a model of chronic 
      neurodegeneration.
FAU - Macauley, Shannon L
AU  - Macauley SL
AD  - Department of Internal Medicine and Genetics, Washington University School of 
      Medicine, St. Louis, Missouri 63110, USA.
FAU - Pekny, Milos
AU  - Pekny M
FAU - Sands, Mark S
AU  - Sands MS
LA  - eng
GR  - R01 NS043205/NS/NINDS NIH HHS/United States
GR  - NS056728/NS/NINDS NIH HHS/United States
GR  - R01 NS043205-08/NS/NINDS NIH HHS/United States
GR  - NS043105/NS/NINDS NIH HHS/United States
GR  - R44 NS043105/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Cytokines)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vimentin)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Astrocytes/*metabolism/*pathology
MH  - Blood-Testis Barrier/physiopathology
MH  - Brain/metabolism/pathology
MH  - Capillary Permeability/genetics
MH  - Cerebral Cortex/pathology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Glial Fibrillary Acidic Protein/deficiency
MH  - Humans
MH  - Infarction, Middle Cerebral Artery/complications
MH  - Intermediate Filaments/genetics/metabolism
MH  - Longevity/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuronal Ceroid-Lipofuscinoses/genetics/*pathology/*physiopathology
MH  - Organ Size/genetics
MH  - RNA, Messenger/metabolism
MH  - Silver Staining
MH  - Thiolester Hydrolases/deficiency
MH  - Up-Regulation/*genetics
MH  - Vimentin/deficiency
PMC - PMC3218425
MID - NIHMS336360
EDAT- 2011/10/28 06:00
MHDA- 2011/12/20 06:00
PMCR- 2012/04/26
CRDT- 2011/10/28 06:00
PHST- 2011/10/28 06:00 [entrez]
PHST- 2011/10/28 06:00 [pubmed]
PHST- 2011/12/20 06:00 [medline]
PHST- 2012/04/26 00:00 [pmc-release]
AID - 31/43/15575 [pii]
AID - 3732973 [pii]
AID - 10.1523/JNEUROSCI.3579-11.2011 [doi]
PST - ppublish
SO  - J Neurosci. 2011 Oct 26;31(43):15575-85. doi: 10.1523/JNEUROSCI.3579-11.2011.