PMID- 17046272
OWN - NLM
STAT- MEDLINE
DCOM- 20070123
LR  - 20181113
IS  - 0969-9961 (Print)
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 25
IP  - 1
DP  - 2007 Jan
TI  - Successive neuron loss in the thalamus and cortex in a mouse model of infantile 
      neuronal ceroid lipofuscinosis.
PG  - 150-62
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the 
      lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated 
      the onset and progression of pathological changes in Ppt1 deficient mice 
      (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical 
      atrophy and neuron loss occurred only late in disease progression but were 
      preceded by localized astrocytosis within individual thalamic nuclei and the 
      progressive loss of thalamic neurons that relay different sensory modalities to 
      the cortex. This thalamic neuron loss occurred first within the visual system and 
      only subsequently in auditory and somatosensory relay nuclei or the inhibitory 
      reticular thalamic nucleus. The loss of granule neurons and GABAergic 
      interneurons followed in each corresponding cortical region, before the onset of 
      seizure activity. These findings provide novel evidence for successive neuron 
      loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an 
      important early focus of INCL pathogenesis.
FAU - Kielar, Catherine
AU  - Kielar C
AD  - Pediatric Storage Disorders Laboratory, Box P040, MRC Social Genetic and 
      Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, 
      King's College London, London, SE5 8AF, UK.
FAU - Maddox, Lucy
AU  - Maddox L
FAU - Bible, Ellen
AU  - Bible E
FAU - Pontikis, Charlie C
AU  - Pontikis CC
FAU - Macauley, Shannon L
AU  - Macauley SL
FAU - Griffey, Megan A
AU  - Griffey MA
FAU - Wong, Michael
AU  - Wong M
FAU - Sands, Mark S
AU  - Sands MS
FAU - Cooper, Jonathan D
AU  - Cooper JD
LA  - eng
GR  - R01 NS043205/NS/NINDS NIH HHS/United States
GR  - NS41930/NS/NINDS NIH HHS/United States
GR  - NS043205/NS/NINDS NIH HHS/United States
GR  - R21 NS041930/NS/NINDS NIH HHS/United States
GR  - R56 NS043205/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061012
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Aging/pathology
MH  - Animals
MH  - Astrocytes/pathology
MH  - Atrophy/pathology
MH  - Cerebral Cortex/*pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Electroencephalography
MH  - Gliosis/pathology
MH  - Interneurons/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microscopy, Fluorescence
MH  - Neuroglia/pathology
MH  - Neuronal Ceroid-Lipofuscinoses/*pathology
MH  - Neurons/*pathology
MH  - Phenotype
MH  - Seizures/etiology
MH  - Synapses/pathology
MH  - Thalamic Nuclei/pathology
MH  - Thalamus/*pathology
MH  - Thiolester Hydrolases/genetics/*physiology
PMC - PMC1866219
MID - NIHMS14439
EDAT- 2006/10/19 09:00
MHDA- 2007/01/24 09:00
PMCR- 2008/02/03
CRDT- 2006/10/19 09:00
PHST- 2006/06/09 00:00 [received]
PHST- 2006/08/29 00:00 [revised]
PHST- 2006/09/03 00:00 [accepted]
PHST- 2006/10/19 09:00 [pubmed]
PHST- 2007/01/24 09:00 [medline]
PHST- 2006/10/19 09:00 [entrez]
PHST- 2008/02/03 00:00 [pmc-release]
AID - S0969-9961(06)00221-X [pii]
AID - 10.1016/j.nbd.2006.09.001 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2007 Jan;25(1):150-62. doi: 10.1016/j.nbd.2006.09.001. Epub 2006 
      Oct 12.