Early immature neuronal death is partially involved in memory impairment induced by cerebral ischemia

Behav Brain Res. 2016 Jul 15:308:75-82. doi: 10.1016/j.bbr.2016.04.019. Epub 2016 Apr 13.

Abstract

Memory impairment is a common after an ischemic stroke. While delayed neuronal death in the CA1 region is usually linked to cerebral ischemia-induced memory impairment, the role of early immature neuronal death within the DG region in the memory state of an ischemic stroke model has rarely been studied. Here, we show a partial role of immature neuronal death in memory impairment in a global ischemia model. We found early immature neuronal death, which was determined by DCX and NeuN-double-staining. Injection of z-DEVD-fmk, a caspase-3 inhibitor, into the DG region rescued cells from immature neuronal death in the DG region without affecting delayed neuronal death in the CA1 region of an ischemic brain. Moreover, z-DEVD-fmk treatment partially rescued ischemia-induced spatial memory impairment. We also found that ischemia-induced LTP impairment in the perforant pathway was restored by z-DEVD-fmk treatment. These results suggest that early immature neuronal death is partially involved in ischemia-induced spatial memory impairment.

Keywords: Immature neuron; Ischemia; Long-term potentiation; Spatial memory.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Ischemia / complications*
  • Caspases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Excitatory Postsynaptic Potentials / drug effects
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / etiology*
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Neuropeptides / metabolism
  • Oligopeptides / pharmacology
  • Phosphopyruvate Hydratase / metabolism
  • Time Factors

Substances

  • Cysteine Proteinase Inhibitors
  • Dcx protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Oligopeptides
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • Caspases
  • Phosphopyruvate Hydratase