Chronic stress exposure following photothrombotic stroke is associated with increased levels of amyloid beta accumulation and altered oligomerisation at sites of thalamic secondary neurodegeneration in mice

Lin Kooi Ong, Zidan Zhao, Murielle Kluge, Frederick R. Walker, Michael Nilsson

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28 Citations (Scopus)

Abstract

Exposure to severe stress following stroke is recognised to complicate the recovery process. We have identified that stress can exacerbate the severity of post-stroke secondary neurodegeneration in the thalamus. In this study, we investigated whether exposure to stress could influence the accumulation of the neurotoxic protein Amyloid-b. Using an experimental model of focal cortical ischemia in adult mice combined with exposure to chronic restraint stress, we examined changes within the contra-and ipsilateral thalamus at six weeks post-stroke using Western blotting and immunohistochemical approaches. Western blotting analysis indicated that stroke was associated with a significant enhancement of the 25 and 50 kDa oligomers within the ipsilateral hemisphere and the 20 kDa oligomer within the contralateral hemisphere. Stroked animals exposed to stress exhibited an additional increase in multiple forms of Amyloid-beta oligomers. Immunohistochemistry analysis confirmed that stroke was associated with a significant accumulation of Amyloid-beta within the thalami of both hemispheres, an effect that was exacerbated in stroke animals exposed to stress. Given that Amyloid-beta oligomers, most notably the 30-40 and 50 kDa oligomers, are recognised to correlate with accelerated cognitive decline, our results suggest that monitoring stress levels in patients recovering from stroke may merit consideration in the future.

Original languageEnglish
Pages (from-to)1338-1348
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 2017
Externally publishedYes

Keywords

  • Amyloid beta
  • Chronic stress
  • Post-stroke
  • Secondary neurodegeneration
  • Thalamus

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