Sökning: id:"swepub:oai:DiVA.org:umu-66572" >
Stress steroids as ...
Stress steroids as accelerators of Alzheimer's disease. : Effects of chronically elevated levels of allopregnanolone in transgenic AD models.
-
- Bengtsson, Sara, 1978- (författare)
- Umeå universitet,Obstetrik och gynekologi,UNC
-
- Wang, Mingde (preses)
- Umeå universitet,Obstetrik och gynekologi
-
- Bäckström, Torbjörn (preses)
- Umeå universitet,Obstetrik och gynekologi
-
visa fler...
-
- Johansson, Maja (preses)
- Umeå universitet,Obstetrik och gynekologi
-
- Graff, Caroline, Professor (opponent)
- Karolinska Institutet, Institutionen för Neurobiologi, Vårdvetenskap och Samhälle
-
visa färre...
-
(creator_code:org_t)
- ISBN 9789174595659
- Umeå : Umeå universitet, 2013
- Engelska 66 s.
-
Serie: Umeå University medical dissertations, 0346-6612 ; 1553
- Relaterad länk:
-
https://umu.diva-por... (primary) (Raw object)
-
visa fler...
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- Background Alzheimer’s disease (AD) and dementia are devastating conditions not only for the affected patients but also for their families. The economical costs for the society are tremendous. Mid-life psychological stress, psychosocial stress and post-traumatic stress disorder cause cognitive dysfunction and lead to increased risk for dementia. However, the mechanisms behind stress-induced AD and dementia are not known. AD is characterized by solid amyloid plaques in the CNS. However, over the last decade it has been concluded that the levels of soluble beta-amyloid (Aβ) correlate to cognitive performance while plaques often do not. The soluble Aβ accumulate intracellularly and disturb the synaptic function. Interestingly, the levels of intracellular Aβ depend on neuronal activity. Previous studies have shown that decreased neuronal activity cause increased intracellular levels of Aβ and cognitive decline. Stress steroids produced in the brain, e.g. allopregnanolone, enhance the activity of the GABAergic system, i.e. the main inhibitory system of the brain. Consequently, allopregnanolone affects neuronal activity. Therefore, it is possible that elevated levels of allopregnanolone (due to e.g. stress) cause increased intracellular levels of Aβ. This could be a mechanism behind stress-induced AD. The purpose of this thesis was to investigate if elevation of allopregnanolone is a possible link in the mechanism behind stress-induced AD by investigating the effects of chronically elevated levels of allopregnanolone in transgenic mouse models for AD.Methods Swe/PS1 and Swe/Arc mice (transgenic models for AD) were treated chronically with elevated allopregnanolone levels, comparable to those at mild stress. After an interval of no treatment, the mice were tested for learning and memory performance in the Morris water maze. The brain tissue of the mice was then analyzed for disease markers, i.e. soluble and insoluble Aβ40 and Aβ42 using enzyme-linked immunosorbent assay, and amyloid plaques using immunohistochemistry and Congo red staining technique. The brain tissue was also analyzed for a marker of synaptic function, i.e. synaptophysin.Results Chronic treatment of allopregnanolone caused impaired learning performance in both the Swe/PS1 and the Swe/Arc mouse models. The Swe/PS1 mice had increased levels of soluble Aβ in both hippocampus and cortex. Interestingly, the levels of soluble Aβ were unchanged in the Swe/Arc mice. Three months of allopregnanolone treatment in the Swe/PS1 mouse model caused decreased plaque size, predominantly in hippocampus. It may be concluded that chronic allopregnanolone elevation caused smaller but more abundant congophilic plaques as both total plaque area and number of plaques were increased in mice with poor learning ability. Additional spots for accumulation of Aβ, predominantly the more toxic Aβ42, and thus additional starting points for plaque production could be a part of the mechanism behind stress-induced Alzheimer’s disease.Conclusions The conclusion of this thesis is that chronic elevation of allopregnanolon accelerated the development of Alzheimer’s disease in the Swe/PS1 and the Swe/Arc transgenic mouse models. Allopregnanolone may be an important link in the mechanism behind stress-induced AD. However, further studies are required to grasp the extent of its pathological influence.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Allopregnanolone
- Alzheimer's disease
- beta-amyloid
- synaptophysin
- chronic stress
- Morris water maze
- obstetrik och gynekologi
- Obstetrics and Gynaecology
- medicinsk farmakologi
- Medical Pharmacology
- Neurology
- neurologi
- Geriatrics
- geriatrik
- medical behavioral science
- medicinsk beteendevetenskap
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
Hitta via bibliotek
Till lärosätets databas