Background
Understanding of the molecular mechanisms of prefrontal cortex (PFC) plasticity is
important for developing new treatment strategies for mental disorders such as depression
and schizophrenia. Long-term potentiation (LTP) is a valid model for synaptic plasticity.
The extracellular proteolytic system composed of matrix metalloproteinases (MMPs)
and their endogenous tissue inhibitors (TIMPs) has recently been shown to play major
role in the hippocampal plasticity.
Methods
We tested whether induction of hippocampal-prefrontal LTP results in accumulation
of tissue inhibitor of MMP-1, TIMP-1 mRNA, in the PFC of rats and whether adenovirally
driven overexpression of TIMP-1 affects LTP. Additional study of slices was done with
a specific MMP-9 inhibitor.
Results
The TIMP-1 is induced in the rat medial PFC by stimuli evoking late LTP; its overexpression
blocks the gelatinolytic activity of the MMP family; its overexpression before tetanization
blocks late LTP in vivo; and MMP-9 inhibitor prevents late LTP in vitro.
Conclusions
We suggest a novel extracellular mechanism of late LTP in the PFC, engaging TIMP-1-controlled
proteolysis as an element of information integration. Our results may also be meaningful
to an understanding of mental diseases and development of new treatment strategies
that are based on extracellular mechanisms of synaptic plasticity.
Key Words
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Article info
Publication history
Published online: January 09, 2007
Accepted:
September 2,
2006
Received in revised form:
August 25,
2006
Received:
April 7,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
