PMID- 17050659
OWN - NLM
STAT- MEDLINE
DCOM- 20071018
LR  - 20070928
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 21
IP  - 6
DP  - 2007 Aug
TI  - Altered expression of synaptic protein mRNAs in STOP (MAP6) mutant mice.
PG  - 635-44
AB  - Stable tubule-only polypeptide (STOP) proteins are a family of microtubule 
      associated proteins (MAPs) important in microtubule stabilization. Data 
      indicating a role for microtubules in synaptic function has come from studies of 
      the STOP null mouse, which exhibits synaptic deficits, in association with 
      behavioural changes that are alleviated by antipsychotic treatment. These 
      findings suggested that STOP mutant mice may be useful in studies of synaptic 
      function, and could be especially relevant to schizophrenia, postulated to be a 
      disorder of the synapse. Moreover, a genetic association between STOP and 
      schizophrenia has been reported. This study aimed to further characterize 
      synaptic alterations in STOP null and heterozygous mice. Using in situ 
      hybridization histochemistry, the mRNA expression of three pre-synaptic 
      (synaptophysin; growth associated protein-43 (GAP-43); vesicular glutamate 
      transporter-1 (VGlut1)) and two post-synaptic (spinophilin; MAP2) proteins, was 
      quantified in female STOP null (n = 7), heterozygous (n = 5) and wild type (n = 
      6) mice. For STOP null and heterozygous mice, synaptophysin, VGlut1, GAP-43 and 
      spinophilin mRNAs were decreased in the hippocampus, whilst in addition in the 
      null mice, synaptophysin, VGlut1 and spinophilin mRNAs were decreased in the 
      cerebellum. Alterations in synaptic protein mRNA expression were also detected in 
      the frontal and occipital cortex. MAP2 mRNA expression was unchanged in all brain 
      regions. The profile of mRNA changes is broadly similar to that observed in 
      schizophrenia. Together the data provide supporting evidence for a role for 
      microtubules in synaptic function, and suggest that STOP, or other microtubule 
      proteins, may contribute to the synaptic pathology of schizophrenia.
FAU - Eastwood, Sharon L
AU  - Eastwood SL
AD  - University of Oxford, Department of Psychiatry, Warneford Hospital, Oxford, UK. 
      sharon.eastwood@psych.ox.ac.uk
FAU - Lyon, Louisa
AU  - Lyon L
FAU - George, Lydia
AU  - George L
FAU - Andrieux, Annie
AU  - Andrieux A
FAU - Job, Didier
AU  - Job D
FAU - Harrison, Paul J
AU  - Harrison PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061018
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (GAP-43 Protein)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Mtap2 protein, mouse)
RN  - 0 (Mtap6 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Slc17a7 protein, mouse)
RN  - 0 (Synaptophysin)
RN  - 0 (Vesicular Glutamate Transport Protein 1)
RN  - 0 (neurabin)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Female
MH  - GAP-43 Protein/metabolism
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microfilament Proteins/metabolism
MH  - Microtubule-Associated Proteins/deficiency/genetics/*metabolism
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - RNA, Messenger/*metabolism
MH  - Schizophrenia/metabolism
MH  - Synapses/*metabolism
MH  - Synaptophysin/metabolism
MH  - Vesicular Glutamate Transport Protein 1/metabolism
EDAT- 2006/10/20 09:00
MHDA- 2007/10/19 09:00
CRDT- 2006/10/20 09:00
PHST- 2006/10/20 09:00 [pubmed]
PHST- 2007/10/19 09:00 [medline]
PHST- 2006/10/20 09:00 [entrez]
AID - 0269881106068825 [pii]
AID - 10.1177/0269881106068825 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2007 Aug;21(6):635-44. doi: 10.1177/0269881106068825. Epub 
      2006 Oct 18.