title: The effects of aging, housing and ibuprofen treatment on brain neurochemistry in a triple transgene Alzheimer's disease mouse model using magnetic resonance spectroscopy and imaging.
abstract: We investigated a triple transgene Alzheimer's disease (AD) mouse model that recapitulates many of the neurochemical, anatomic, pathologic and behavioral defects seen in human AD. We studied the mice as a function of age and brain region and investigated potential therapy with the non-steroidal anti-inflammatory drug ibuprofen. Magnetic resonance spectroscopy (MRS) showed alterations characteristic of AD (i.e. increased myo-inositol and decreased N-acetylaspartate (NAA)). Mice at 6 months of age showed an increase in myo-inositol in the hippocampus at a time when the Aβ is intracellular, but not in amygdala or cortex. Myo-inositol increased as a function of age in the amygdala, cortex and striatum while NAA decreased only in the hippocampus and cortex at 17-23 months of age. Ibuprofen protected the increase of myo-inositol at six months of age in the hippocampus, but had no effect at 17-23 months of age (a time when Aβ is extracellular). In vivo MRI and MRS showed that at 17-23 months of age there was a significant protective effect of ibuprofen on hippocampal volume and NAA loss. Together, these data show the following: the increase in myo-inositol occurs before the decrease in NAA in hippocampus but not cortex; the hippocampus shows earlier changes than does the amygdale or cortex consistent with earlier deposition of Aβ40-42 in the hippocampus and ibuprofen protects against multiple components of the AD pathology. These data also show a profound effect of housing on this particular mouse model.
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: jchoi@nmr.mgh.harvard.edu.
authors.forename: Ji-Kyung
authors.initials: JK
authors.lastname: Choi
authors.affiliation: Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Carreras
authors.affiliation: Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Nur
authors.initials: N
authors.lastname: Aytan
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Jenkins-Sahlin
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Alpaslan
authors.initials: A
authors.lastname: Dedeoglu
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: bgj@nmr.mgh.harvard.edu.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Jenkins
mesh_terms: D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000235:genetics*; D000679:Amygdala / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006799:Housing, Animal; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019076:Transgenes / Q000235:genetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen
keywords: Alzheimer’s disease; Animal model; Magnetic resonance imaging; Magnetic resonance spectroscopy; Triple transgene