Kurzfassung

Changes in components of the endocannabinoid system (ECS) in the brains of Alzheimer’s Disease (AD) patients, such as a reduction of CB1 receptor positive neurons in AD-affected brain regions, prompted us to investigate the potential interaction of the ECS with AD. To modulate the ECS in an AD mouse we crossed CB1-deficient mice with APP23 mice, a well described AD mouse model showing not only overexpression of mutated human APP (amyloid precursor protein), higher levels of toxic Aβ peptides...Changes in components of the endocannabinoid system (ECS) in the brains of Alzheimer’s Disease (AD) patients, such as a reduction of CB1 receptor positive neurons in AD-affected brain regions, prompted us to investigate the potential interaction of the ECS with AD. To modulate the ECS in an AD mouse we crossed CB1-deficient mice with APP23 mice, a well described AD mouse model showing not only overexpression of mutated human APP (amyloid precursor protein), higher levels of toxic Aβ peptides and amyloid plaques but also learning and memory deficits in several tests. For APP23/CB1-/- mice we found a lower birth rate and an increased mortality compared to their APP23/CB1+/- counterparts. Despite a reduced expression of APP and a reduced amyloid plaque load, APP23/CB1-/- mice showed decreased learning and memory capabilities. We will now study possible alterations in these mice at an anatomical, cellular and molecular level. Here, we are particularly interested in the involvement of oxidative stress, the degree of myelination in various brain regions and a role of protein degradation pathways as an induction of autophagy by cannabinoids has been demonstrated recently. In cell culture experiments expression, intracellular transport, maturation and processing of APP will be analyzed in detail.

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