A role for myotonic dystrophy protein kinase in synaptic plasticity.
Myotonic dystrophy (DM) is associated with an expanded triplet repeat in the 3'-untranslated region of the gene for myotonic dystrophy protein kinase (DMPK), which may reduce DMPK expression. It is unclear how reduced DMPK expression might contribute to the symptoms of DM because the normal function of DMPK is not yet understood. Thus we investigated the function of DMPK to gain insight into how reduced DMPK expression might lead to cognitive dysfunction in DM. We recently demonstrated a role for DMPK in modifying the cytoskeleton, and remodeling of the cytoskeleton is thought to be important for cognitive function. Therefore we hypothesized that DMPK might normally contribute to synaptic plasticity and cognitive function via an effect on actin cytoskeletal rearrangements. To test for involvement of DMPK in synaptic plasticity, we utilized the DMPK null mouse. This mouse showed no changes in baseline synaptic transmission in hippocampal area CA1, nor any changes in long-term synaptic potentiation (LTP) measured 3 h after induction. There was a significant decrease, however, in the decremental potentiation with a duration of 30-180 min that accompanies LTP. These results suggest a role for DMPK in synaptic plasticity that could be relevant to the cognitive dysfunction associated with DM.
Schulz
Paul E
PE
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA. pschulz@bcm.tmc.edu
McIntosh
Adeka D
AD
Kasten
Michael R
MR
Wieringa
Berend
B
Epstein
Henry F
HF
D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009223:Myotonic Dystrophy / Q000235:genetics / Q000503:physiopathology*; D065636:Myotonin-Protein Kinase; D009473:Neuronal Plasticity / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
C585516:DMPK protein, mouse; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases