PMID- 17656100
OWN - NLM
STAT- MEDLINE
DCOM- 20071212
LR  - 20131121
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 28
IP  - 1
DP  - 2007 Oct
TI  - Palmitoyl protein thioesterase 1 (Ppt1)-deficient mouse neurons show alterations 
      in cholesterol metabolism and calcium homeostasis prior to synaptic dysfunction.
PG  - 52-64
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative 
      disorder of children, characterized by selective death of neocortical neurons. To 
      understand early disease mechanisms in INCL, we have studied Ppt1(Deltaex4) 
      knock-out mouse neurons in culture and acute brain slices. Global transcript 
      profiling showed deregulation of key neuronal functions in knock-out mice 
      including cholesterol metabolism, neuronal maturation, and calcium homeostasis. 
      Cholesterol metabolism showed major changes; sterol biosynthesis was enhanced and 
      steady-state amounts of sterols were altered at the cellular level. Changes were 
      also present in early maturation of Ppt1(Deltaex4) neurons indicated by increased 
      proliferative capacity of neuronal stem cells. Knock-out neurons presented 
      unaltered electrophysiological properties suggesting uncompromised synaptic 
      function in young animals. However, knock-out neurons exhibited more efficient 
      recovery from glutamate-induced calcium transients, possibly indicating 
      neuroprotective activation. This study established that the neuronal deregulation 
      in INCL is linked to neuronal maturation, lipid metabolism and calcium 
      homeostasis.
FAU - Ahtiainen, Laura
AU  - Ahtiainen L
AD  - National Public Health Institute, Department of Molecular Medicine, Biomedicum 
      Helsinki, PO Box 104, 00251 Helsinki, Finland.
FAU - Kolikova, Julia
AU  - Kolikova J
FAU - Mutka, Aino-Liisa
AU  - Mutka AL
FAU - Luiro, Kaisu
AU  - Luiro K
FAU - Gentile, Massimiliano
AU  - Gentile M
FAU - Ikonen, Elina
AU  - Ikonen E
FAU - Khiroug, Leonard
AU  - Khiroug L
FAU - Jalanko, Anu
AU  - Jalanko A
FAU - Kopra, Outi
AU  - Kopra O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070623
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Cholesterol/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Profiling
MH  - Hippocampus/metabolism
MH  - *Homeostasis
MH  - Mice
MH  - Mice, Congenic
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuronal Ceroid-Lipofuscinoses/physiopathology
MH  - Neurons/cytology/*metabolism
MH  - Organ Culture Techniques
MH  - Patch-Clamp Techniques
MH  - Stem Cells/cytology
MH  - Synapses/metabolism/pathology
MH  - Thiolester Hydrolases/*deficiency/genetics
EDAT- 2007/07/28 09:00
MHDA- 2007/12/13 09:00
CRDT- 2007/07/28 09:00
PHST- 2007/03/22 00:00 [received]
PHST- 2007/05/30 00:00 [revised]
PHST- 2007/06/08 00:00 [accepted]
PHST- 2007/07/28 09:00 [pubmed]
PHST- 2007/12/13 09:00 [medline]
PHST- 2007/07/28 09:00 [entrez]
AID - S0969-9961(07)00133-7 [pii]
AID - 10.1016/j.nbd.2007.06.012 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2007 Oct;28(1):52-64. doi: 10.1016/j.nbd.2007.06.012. Epub 2007 
      Jun 23.