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The impact of reproductive axis hormones on changes in brain functional networks during healthy, accelerated and pathological aging (i.e. Alzheimer's disease).

Aging has profound effects on many cellular processes that predispose to neurodegeneration, impairment in cognitive function, as well as changes in brain functional networks (e.g. default mode network (DMN) and its anticorrelated networks) and synaptic alterations. However, the key mechanisms orchestrating brain aging remain largely unknown. The hypothalamus, a key region of the hypothalamic–pituitary–gonadal axis (HPG-axis), is crucial for the neuroendocrine interaction between the central nervous system and various peripheral functions, but seems also involved in age-related neurodegeneration. This knowledge drives a new paradigm shift suggesting that the aging process is driven by the integration of immune and hormonal responses, with the hypothalamus having a leading role. A broad literature also suggests the involvement of menopause and age-related testosterone decline-induced alterations in HPG axis hormone levels in the etiology of Alzheimer's disease (AD), which is the most common form of dementia in elderly population. The overall goal of this preclinical project is to investigate patterns of functional alterations in the DMN and its anticorrelated networks using rsfMRI across from normal aging to accelerated and pathological aging (i.e, AD), and to explore whether differences in functional connectivity are associated with differences in HPG axis hormones and hypothalamic inflammation. The first aim of the study is to observe the short and long term effect of luteinizing hormone (LH) and estrogen hormone treatment, on the DMN and its anticorrelated networks. We hypothesize that loss of estrogenic support after ovariectomy will have significant effect on these networks, and these effect can be reversed after hormone therapy. The second aim of the project is to gain more insight into how the alterations of the GnRH-HPG axis receptor signalling alter functional networks of the brain during pathological aging (i.e. AD). The third aim is to examine the capacity of a GnRH agonist, leuprolide acetate, which decreases the release of LH, and amyloid load to modulate DMN and its anticorrelated networks, in the brain of Tg2576 carrying Swedish APP mutation.
Date:1 Nov 2014  →  31 Oct 2018
Disciplines:Multimedia processing, Biological system engineering, Signal processing, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing