PMID- 15562504
OWN - NLM
STAT- MEDLINE
DCOM- 20050315
LR  - 20131121
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 481
IP  - 2
DP  - 2005 Jan 10
TI  - Phenotype of cerebellar glutamatergic neurons is altered in stargazer mutant mice 
      lacking brain-derived neurotrophic factor mRNA expression.
PG  - 145-59
AB  - Brain-derived neurotrophic factor (BDNF) influences neuronal survival, 
      differentiation, and maturation. More recently, its role in synapse formation and 
      plasticity has also emerged. In the cerebellum of the spontaneous recessive 
      mutant mouse stargazer (stg) there is a specific and pronounced deficit in BDNF 
      mRNA expression. BDNF protein levels in the cerebellum as a whole are reduced by 
      70%, while in the granule cells (GCs) there is a selective and near total 
      reduction in BDNF mRNA expression. Recently, we published data demonstrating that 
      inhibitory neurons in the cerebella of stgs have significantly reduced levels 
      (approximately 50%) of gamma-aminobutyric acid (GABA) and fewer, smaller 
      inhibitory synapses compared to wildtype (WT) controls. Our current 
      investigations indicate that the stargazer mutation has an even more pronounced 
      effect on the phenotype of glutamatergic neurons in the cerebellum. There is a 
      profound decrease in the levels of glutamate-immunoreactivity (up to 77%) in stg 
      compared to WT controls. The distribution profile of presynaptic vesicles is also 
      markedly different: stgs have proportionally fewer docked vesicles and fewer 
      vesicles located adjacent to the active zone ready to dock than WTs. Furthermore, 
      the thickness of the postsynaptic density (PSD) at mossy fiber-granule cell 
      (MF-GC) and parallel fiber-Purkinje cell (PF-PC) synapses is severely reduced (up 
      to 33% less than WT controls). The number and length of excitatory synapses, 
      however, appear to be relatively unchanged. It is possible that at least some of 
      theses changes in phenotype are directly attributable to the lack of BDNF in the 
      cerebellum of the stg mutant.
CI  - 2004 Wiley-Liss, Inc.
FAU - Richardson, Christine A
AU  - Richardson CA
AD  - School of Biological & Biomedical Sciences, University of Durham, Durham DH1 3LE, 
      United Kingdom.
FAU - Leitch, Beulah
AU  - Leitch B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/deficiency/*genetics
MH  - Cerebellum/*abnormalities/*metabolism/ultrastructure
MH  - Female
MH  - Gene Expression Regulation, Developmental/genetics
MH  - Glutamic Acid/metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Neurologic Mutants
MH  - Microscopy, Electron, Transmission
MH  - Mutation/*genetics
MH  - Nerve Fibers/metabolism/ultrastructure
MH  - Neuronal Plasticity/genetics
MH  - Neurons/*metabolism/ultrastructure
MH  - Phenotype
MH  - Purkinje Cells/metabolism/ultrastructure
MH  - RNA, Messenger/metabolism
MH  - Synaptic Membranes/metabolism/ultrastructure
MH  - Synaptic Transmission/genetics
MH  - Synaptic Vesicles/metabolism/ultrastructure
EDAT- 2004/11/25 09:00
MHDA- 2005/03/16 09:00
CRDT- 2004/11/25 09:00
PHST- 2004/11/25 09:00 [pubmed]
PHST- 2005/03/16 09:00 [medline]
PHST- 2004/11/25 09:00 [entrez]
AID - 10.1002/cne.20386 [doi]
PST - ppublish
SO  - J Comp Neurol. 2005 Jan 10;481(2):145-59. doi: 10.1002/cne.20386.