Open AccessEnvironmental Enrichment Counteracts Alzheimer’s Neurovascular Dysfunction in TgCRND8 Mice
Author(s) -
Herring Arne,
Yasin Hamzah,
Ambrée Oliver,
Sachser Norbert,
Paulus Werner,
Keyvani Kathy
Publication year - 2008
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2007.00094.x
Subject(s) - environmental enrichment , neuroscience , lrp1 , cerebral amyloid angiopathy , alzheimer's disease , genetically modified mouse , neurovascular bundle , amyloid precursor protein , transgene , biology , disease , medicine , dementia , endocrinology , anatomy , biochemistry , gene , lipoprotein , ldl receptor , cholesterol
We and others have recently demonstrated that cognitive and physical stimulation in form of environmental enrichment reduces cerebral β‐amyloid (Aβ) 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 Aβ. 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 Aβ receptor/transporter molecules, namely up‐regulation of LRP1, ApoE and A2M as well as down‐regulation of RAGE so that brain to blood Aβ clearance is facilitated. These results suggest a hitherto unknown effect of environmental enrichment counteracting the vascular dysfunction in Alzheimer diseased brain.