Ungless, MA

Journal of Neuroscience

English

Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is
implicated in a number of brain disorders, including Alzheimer’s disease. Thus there is great
interest in understanding the signalling systems that control MAPK function. One family of
proteins that contribute to this process, the mitogen-activated protein kinase phosphatases
(MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have
identified novel functions of MKPs in development, the immune system and cancer.
However, a significant gap in our knowledge remains in relation to their role in brain
functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been
knocked out (MKP-2-/- mice), we show that long-term potentiation (LTP) is impaired in
MKP-2-/-
mice compared to MKP-2+/+ controls whereas neuronal excitability, evoked synaptic
transmission and paired-pulse facilitation remain unaltered. Furthermore, spontaneous
excitatory postsynaptic currents (sEPSC) frequency was increased in acute slices and primary
hippocampal cultures prepared from MKP-2-/- mice with no effect on EPSC amplitude
observed. An increase in synapse number was evident in primary hippocampal cultures
which may account for the increase in spontaneous EPSC frequency. In addition no change in
ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting
that the effects of MKP-2 deletion were MAPK independent. Consistent with these
alterations in hippocampal function, MKP-2-/- mice show deficits in spatial reference and
working memory when investigated using the Morris water maze. These data show that
MKP-2 plays a role in regulating hippocampal function and that this effect may be
independent of MAPK signalling

Spiral - Imperial College Digital Repository

Mitogen-activated protein kinase phosphatase-2 deletion impairs synaptic plasticity and hippocampal-dependent memory

http://spiral.imperial.ac.uk/bitstream/10044/1/29222/9/2348.full.pdf

Mitogen-activated protein kinase phosphatase-2 deletion impairs synaptic plasticity and hippocampal-dependent memory

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