Structural Plasticity of Dendritic Spines Requires GSK3α and GSK3β

PLoS One. 2015 Jul 24;10(7):e0134018. doi: 10.1371/journal.pone.0134018. eCollection 2015.

Abstract

Although memories appear to be elusive phenomena, they are stored in the network of physical connections between neurons. Dendritic spines, which are actin-rich dendritic protrusions, serve as the contact points between networked neurons. The spines' shape contributes to the strength of signal transmission. To acquire and store information, dendritic spines must remain plastic, i.e., able to respond to signals, by changing their shape. We asked whether glycogen synthase kinase (GSK) 3α and GSK3β, which are implicated in diseases with neuropsychiatric symptoms, such as Alzheimer's disease, bipolar disease and schizophrenia, play a role in a spine structural plasticity. We used Latrunculin B, an actin polymerization inhibitor, and chemically induced Long-Term Depression to trigger fast spine shape remodeling in cultured hippocampal neurons. Spine shrinkage induced by either stimulus required GSK3α activity. GSK3β activity was only important for spine structural changes after treatment with Latrunculin B. Our results indicate that GSK3α is an essential component for short-term spine structural plasticity. This specific function should be considered in future studies of neurodegenerative diseases and neuropsychiatric conditions that originate from suboptimal levels of GSK3α/β activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cells, Cultured
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Hippocampus / cytology
  • Hippocampus / embryology
  • Mice
  • Neurogenesis*
  • Thiazolidines / pharmacology

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Thiazolidines
  • Glycogen Synthase Kinase 3
  • latrunculin B

Grant support

This research was supported by the Polish National Science Centre—(http://www.ncn.gov.pl/) (2011/01/M/NZ3/05413, 2011/01/B/NZ3/05397 and 2011/01/N/NZ3/05409), ERA-NET NEURON/06/2011 - (http://www.neuron-eranet.eu) (co-financed by NCRD) and FP7 European Union grant (#223276, “NeuroGSK3”). JJ is a recipient of "Mistrz" Professorial subsidy from the Foundation for Polish Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.