Differential Tiam1/Rac1 activation in hippocampal and cortical neurons mediates differential spine shrinkage in response to oxygen/glucose deprivation.

Elena Blanco Suarez, Maria Fiuza, Xun Liu, Ela Chakkarapani, Jonathan Hanley

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Citations (Scopus)
305 Downloads (Pure)

Abstract

Distinct neuronal populations show differential sensitivity to global ischemia, with hippocampal CA1 neurons showing greater vulnerability compared to cortical neurons. The mechanisms that underlie differential vulnerability are unclear, and we hypothesize that intrinsic differences in neuronal cell biology are involved. Dendritic spine morphology changes in response to ischemic insults in vivo, but cell type-specific differences and the molecular mechanisms leading to such morphologic changes are unexplored. To directly compare changes in spine size in response to oxygen/glucose deprivation (OGD) in cortical and hippocampal neurons, we used separate and equivalent cultures of each cell type. We show that cortical neurons exhibit significantly greater spine shrinkage compared to hippocampal neurons. Rac1 is a Rho-family GTPase that regulates the actin cytoskeleton and is involved in spine dynamics. We show that Rac1 and the Rac guanine nucleotide exchange factor (GEF) Tiam1 are differentially activated by OGD in hippocampal and cortical neurons. Hippocampal neurons express more Tiam1 than cortical neurons, and reducing Tiam1 expression in hippocampal neurons by shRNA enhances OGD-induced spine shrinkage. Tiam1 knockdown also reduces hippocampal neuronal vulnerability to OGD. This work defines fundamental differences in signalling pathways that regulate spine morphology in distinct neuronal populations that may have a role in the differential vulnerability to ischemia.
Original languageEnglish
Pages (from-to)1898-1906
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number12
Early online date24 Sep 2014
DOIs
Publication statusPublished - Dec 2014

Bibliographical note

Date of Acceptance: 20/08/2014

Keywords

  • cell death
  • cortex
  • dendritic spine
  • hippocampus
  • ischemia
  • OGD

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