Abstract
We and others have recently demonstrated that cognitive and physical stimulation in form of environmental enrichment reduces cerebral beta-amyloid (Abeta) deposition in transgenic mouse models of Alzheimer's disease. This effect was independent from amyloid precursor protein (APP) expression or processing and rather a consequence of enhanced clearance of Abeta. However, the detailed mechanisms remain unclear. In the present study, we show that environmental enrichment in TgCRND8 mice (carrying human APP(Swedish+Indiana)) affect the neurovascular unit by increased angiogenesis and differential regulation of Abeta receptor/transporter molecules, namely up-regulation of LRP1, ApoE and A2M as well as down-regulation of RAGE so that brain to blood Abeta clearance is facilitated. These results suggest a hitherto unknown effect of environmental enrichment counteracting the vascular dysfunction in Alzheimer diseased brain.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alzheimer Disease / physiopathology
-
Alzheimer Disease / prevention & control
-
Alzheimer Disease / therapy*
-
Amyloid beta-Peptides / metabolism
-
Amyloid beta-Protein Precursor / genetics
-
Amyloid beta-Protein Precursor / metabolism
-
Animals
-
Carrier Proteins / metabolism
-
Cerebral Arteries / metabolism*
-
Cerebral Arteries / pathology
-
Cerebral Arteries / physiopathology
-
Cerebrovascular Circulation / physiology
-
Cerebrovascular Disorders / physiopathology
-
Cerebrovascular Disorders / prevention & control
-
Cerebrovascular Disorders / therapy*
-
Cricetinae
-
Disease Models, Animal
-
Environment Design*
-
Female
-
Gene Expression Regulation / physiology
-
Housing, Animal
-
Humans
-
Mice
-
Mice, Transgenic
-
Microcirculation / metabolism
-
Microcirculation / pathology
-
Microcirculation / physiopathology
-
Mitogen-Activated Protein Kinases / metabolism
-
Neovascularization, Physiologic
-
Treatment Outcome
Substances
-
Amyloid beta-Peptides
-
Amyloid beta-Protein Precursor
-
Carrier Proteins
-
Mok protein, mouse
-
Mitogen-Activated Protein Kinases