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Pathogenic mechanisms
B11 Long-term alterations in dendritic spine stability in huntington disease: mechanisms underlying learning deficits in huntington disease?
  1. RP Murmu,
  2. J-y Li
  1. Wallenberg Neuroscience Center, Neural Plasticity and Repair, Lund University, Lund, Sweden

Abstract

Background Huntington's disease (HD) is inherited neurodegenerative disorder characterised by involuntary motor abnormalities and by cognitive deficits. The motor symptoms in HD are caused by degeneration of neurons in the striatum and cerebral cortex, which have died up to 40%–60% when the symptoms are diagnosed. Hence, cell death appears to be relatively late phenomena in Huntington disease. On the other hand, cognitive deficits such as, learning and memory problems precede the overt motor symptoms and cell death by years in HD patients and in animal models suggesting that abnormalities in synaptic functions may underlie the early symptoms. Increasing evidences suggest HD as a synaptopathy.

Aims The aim of this study is to determine whether the dynamics of dendritic spines (post-synaptic structure) is altered in HD.

Method/techniques We use in vivo time-lapse imaging with 2-photon microscopy through cranial window to study dendritic spine dynamics in HD.

Result/outcome Our result suggests that R6/2 mice display altered spine dynamics in layer II/III cortical neurons compared to controls. In the R6/2 mice as the disease progressed we noticed the loss of persistent type spines. Additionally, the density of transient spines was increased in R6/2 mice compare to controls. R6/2 mice also display increased dendritic spine turnover and decreased spine density in their cortical neurons compared to controls.

Conclusions The altered spine dynamics in R6/2 mice would lead to defective synaptic transmission, which may underlie the early symptoms of the disease such as the learning and memory deficits observed in Huntington disease.

  • Synaptic alterations
  • dendritic spines
  • Huntington disease
  • learning and memory deficits

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