Ouabain increases neuronal branching in hippocampus and improves spatial memory

Neuropharmacology. 2018 Sep 15:140:260-274. doi: 10.1016/j.neuropharm.2018.08.008. Epub 2018 Aug 9.

Abstract

Previous research shows Ouabain (OUA) to bind Na, K-ATPase, thereby triggering a number of signaling pathways, including the transcription factors NFᴋB and CREB. These transcription factors play a key role in the regulation of BDNF and WNT-β-catenin signaling cascades, which are involved in neuroprotection and memory regulation. This study investigated the effects of OUA (10 nM) in the modulation of the principal signaling pathways involved in morphological plasticity and memory formation in the hippocampus of adult rats. The results show intrahippocampal injection of OUA 10 nM to activate the Wnt/β-Catenin signaling pathway and to increase CREB/BDNF and NFᴋB levels. These effects contribute to important changes in the cellular microenvironment, resulting in enhanced levels of dendritic branching in hippocampal neurons, in association with an improvement in spatial reference memory and the inhibition of long-term memory extinction.

Keywords: BDNF; Dendritic branching; Hippocampus; Ouabain; Reference memory; Wnt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axin Protein / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Hippocampus / cytology*
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Male
  • Maze Learning
  • Microinjections
  • NF-kappa B / metabolism
  • Neoplasm Proteins / metabolism
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Ouabain / pharmacology*
  • Rats
  • Spatial Memory / drug effects*
  • Spatial Memory / physiology
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / physiology
  • beta Catenin / metabolism

Substances

  • Axin Protein
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • NF-kappa B
  • Neoplasm Proteins
  • Nucleocytoplasmic Transport Proteins
  • beta Catenin
  • p65 oncofetal mRNA transport protein, rat
  • Ouabain