Environmental enrichment counteracts Alzheimer's neurovascular dysfunction in TgCRND8 mice.
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.
Herring
Arne
A
Institute of Neuropathology, University Hospital, University of Münster, Münster, Germany.
Yasin
Hamzah
H
Ambrée
Oliver
O
Sachser
Norbert
N
Paulus
Werner
W
Keyvani
Kathy
K
D000544:Alzheimer Disease / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D006224:Cricetinae; D004195:Disease Models, Animal; D004779:Environment Design; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006799:Housing, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; C498977:Mok protein, mouse; D020928:Mitogen-Activated Protein Kinases