title: Increased blood-brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model.
abstract: Behavioral and psychological problems are often observed in patients with dementia such as that associated with Alzheimer disease, and these noncognitive symptoms place an extremely heavy burden on the family and caregivers. Although it is well know that these symptoms often are triggered by infection of peripheral organs, the underlying mechanisms for these pathological conditions are still unclear. In this study, using an Alzheimer amyloid precursor protein (APP)-transgenic mouse, we analyzed behavioral changes and brain inflammatory response induced by peripheral administration of lipopolysaccharide. Application of a unique in vivo microdialysis system revealed that the increase in brain inflammatory cytokine (interleukin-6) level was significantly higher in APP-Tg than in wild-type mice after peripheral lipopolysaccharide injection, which was associated with more severe sickness behaviors. The blood-brain barrier became more permeable in APP-Tg mice during peripherally evoked inflammation, suggesting the increased vulnerability of the blood-brain barrier to inflammation in this animal model of Alzheimer's disease. These findings might provide insight into the pathogenesis of noncognitive symptoms in dementia and a basis to develop new therapeutic treatments for them.
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Takeda
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ikimura
authors.forename: Hirohito
authors.initials: H
authors.lastname: Nishino
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy
chemical_list: D016564:Amyloid beta-Protein Precursor; D015850:Interleukin-6; D008070:Lipopolysaccharides; C577686:interleukin-6, mouse