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Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice.

Publication ,  Journal Article
Chen, Y; Milenkovic, M; Horsfall, W; Salahpour, A; Soderling, SH; Ramsey, AJ
Published in: PLoS One
2018

NMDA receptors are important for cognition and are implicated in neuropsychiatric disorders. GluN1 knockdown (GluN1KD) mice have reduced NMDA receptor levels, striatal spine density deficits, and cognitive impairments. However, how NMDA depletion leads to these effects is unclear. Since Rho GTPases are known to regulate spine density and cognition, we examined the levels of RhoA, Rac1, and Cdc42 signaling proteins. Striatal Rac1-pathway components are reduced in GluN1KD mice, with Rac1 and WAVE-1 deficits at 6 and 12 weeks of age. Concurrently, medium spiny neuron (MSN) spine density deficits are present in mice at these ages. To determine whether WAVE-1 deficits were causal or compensatory in relation to these phenotypes, we intercrossed GluN1KD mice with WAVE-1 overexpressing (WAVE-Tg) mice to restore WAVE-1 levels. GluN1KD-WAVE-Tg hybrids showed rescue of striatal WAVE-1 protein levels and MSN spine density, as well as selective behavioral rescue in the Y-maze and 8-arm radial maze tests. GluN1KD-WAVE-Tg mice expressed normalized WAVE-1 protein levels in the hippocampus, yet spine density of hippocampal CA1 pyramidal neurons was not significantly altered. Our data suggest a nuanced role for WAVE-1 effects on cognition and a delineation of specific cognitive domains served by the striatum. Rescue of striatal WAVE-1 and MSN spine density may be significant for goal-directed exploration and associated long-term memory in mice.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2018

Volume

13

Issue

10

Start / End Page

e0199341

Location

United States

Related Subject Headings

  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • Wiskott-Aldrich Syndrome Protein Family
  • Transgenes
  • Signal Transduction
  • Receptors, N-Methyl-D-Aspartate
  • Phenotype
  • Neuropeptides
  • Nerve Tissue Proteins
  • Mice, Knockout
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, Y., Milenkovic, M., Horsfall, W., Salahpour, A., Soderling, S. H., & Ramsey, A. J. (2018). Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice. PLoS One, 13(10), e0199341. https://doi.org/10.1371/journal.pone.0199341
Chen, Yuxiao, Marija Milenkovic, Wendy Horsfall, Ali Salahpour, Scott H. Soderling, and Amy J. Ramsey. “Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice.PLoS One 13, no. 10 (2018): e0199341. https://doi.org/10.1371/journal.pone.0199341.
Chen Y, Milenkovic M, Horsfall W, Salahpour A, Soderling SH, Ramsey AJ. Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice. PLoS One. 2018;13(10):e0199341.
Chen, Yuxiao, et al. “Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice.PLoS One, vol. 13, no. 10, 2018, p. e0199341. Pubmed, doi:10.1371/journal.pone.0199341.
Chen Y, Milenkovic M, Horsfall W, Salahpour A, Soderling SH, Ramsey AJ. Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice. PLoS One. 2018;13(10):e0199341.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2018

Volume

13

Issue

10

Start / End Page

e0199341

Location

United States

Related Subject Headings

  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • Wiskott-Aldrich Syndrome Protein Family
  • Transgenes
  • Signal Transduction
  • Receptors, N-Methyl-D-Aspartate
  • Phenotype
  • Neuropeptides
  • Nerve Tissue Proteins
  • Mice, Knockout