PMID- 16201992
OWN - NLM
STAT- MEDLINE
DCOM- 20051027
LR  - 20071114
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 46 Suppl 7
DP  - 2005
TI  - Disruption of interneuron development.
PG  - 22-8
AB  - Disruption of gamma-aminobutyric acid (GABAergic) interneuron development during 
      the embryonic and early postnatal periods can have profound neurological and 
      behavioral consequences. Hepatocyte growth factor/scatter factor (HGF/SF) has 
      been identified as an important molecular cue that may guide the movement of 
      interneurons from their birthplace in the ganglionic eminences (GE) to their 
      final resting place in the neocortex. In vitro studies demonstrate that decreased 
      HGF/SF bioactivity in pallial and subpallial tissues is associated with a 
      reduction in the number of cells migrating out of GE explants. The uPAR knockout 
      mouse provides a unique opportunity to study the effects of interneuron 
      disruption in vivo. uPAR-/- mice have reduced HGF/SF bioactivity in the GE during 
      the period of interneuron development and a concomitant 50% reduction in the 
      number of GABAergic interneurons seeding frontal and parietal regions of the 
      cerebral cortex. Behaviorally, these mice display an increased susceptibility to 
      seizures, heightened anxiety, and diminished social interaction. This article 
      discusses the commonalities between the functional defects seen in uPAR-/- mice 
      and those of humans with developmental disorders, such as epilepsy, 
      schizophrenia, and autism. It is suggested that disruption of GABAergic 
      interneuron development may represent a common point of convergence underlying 
      the etiologies of many of these developmental disorders.
FAU - Levitt, Pat
AU  - Levitt P
AD  - Vanderbilt University, Vanderbilt Kennedy Center for Research on Human 
      Development, Nashville, Tennessee 37203, USA. Pat.levitt@vanderbilt.edu
LA  - eng
GR  - MH652 99/MH/NIMH NIH HHS/United States
GR  - P30 HD15052/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Autistic Disorder/physiopathology
MH  - Behavior, Animal/physiology
MH  - Cell Division/genetics/physiology
MH  - Cell Movement/genetics/physiology
MH  - Cerebral Cortex/cytology/*physiopathology
MH  - Disease Models, Animal
MH  - Electroencephalography/statistics & numerical data
MH  - Epilepsy/genetics/pathology/*physiopathology
MH  - Hepatocyte Growth Factor/physiology
MH  - Humans
MH  - Interneurons/*physiology
MH  - Maze Learning/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation/genetics
MH  - Phenotype
MH  - Pyramidal Cells/cytology/physiopathology
MH  - Schizophrenia/physiopathology
MH  - Synaptic Transmission/genetics/physiology
MH  - gamma-Aminobutyric Acid/*physiology
EDAT- 2005/10/06 09:00
MHDA- 2005/10/28 09:00
CRDT- 2005/10/06 09:00
PHST- 2005/10/06 09:00 [pubmed]
PHST- 2005/10/28 09:00 [medline]
PHST- 2005/10/06 09:00 [entrez]
AID - EPI305 [pii]
AID - 10.1111/j.1528-1167.2005.00305.x [doi]
PST - ppublish
SO  - Epilepsia. 2005;46 Suppl 7:22-8. doi: 10.1111/j.1528-1167.2005.00305.x.