The effect of Alzheimer’s disease on cognitive decline after an ischemic stroke and the role of neurogenesis.

Project Details

Description

Ischemic stroke (IS) and Alzheimer’s disease (AD) are both common neurological diseases. IS can be defined as the sudden onset of a focal neurological deficit due to loss of regional blood supply. AD manifests by core features of progressive memory impairment, visuospatial decline and loss of executive functions. Cognitive worsening in general and an increased rate of cognitive decline in AD patients after stroke has already been reported. In both AD and IS, neurogenesis seems to play an important role. After IS, aberrant neurogenesis seems to interfere with the existing hippocampal circuitry and can therefore influence cognitive functioning. We hypothesize that stroke-induced cognitive decline is more pronounced in AD mice than in WT controls as a result of aberrant neurogenesis.
This hypothesis will be tested in an animal study using a well-established AD (3xTg) mouse model, a stroke mouse model by middle cerebral artery occlusion (MCAO) and a combined model. We will investigate the role of neurogenesis after stroke in AD mice and how their cognitive performance in memory tasks is influenced. To this purpose, temozolomide (TMZ, inhibitor of neurogenesis) and memantine (MEM, stimulator of neurogenesis) will be administered.
We will assess the effect of both treatments on cognitive performance and various markers of AD progression, neurodegeneration, inflammation and neurogenesis. If successful, a future similar clinical investigation could be set up.
Acronymfwotm1015
StatusActive
Effective start/end date1/11/2031/10/22

Keywords

  • Neurogenesis in focal cerebral ischemia and Alzheimer’s disease.
  • The murine middle cerebral artery occlusion model for focal cerebral ischemia.
  • The triple transgenic mouse model for Alzheimer’s disease.
  • Effects of neurogenesis on cognitive decline

Flemish discipline codes

  • Cognitive neuroscience
  • Behavioural neuroscience
  • Neurological and neuromuscular diseases