title: Hippocampal neurochemical changes in senescent mice induced with chronic injection of D-galactose and NaNO₂: an in vitro high-resolution NMR spectroscopy study at 9.4T.
abstract: Proton magnetic resonance spectroscopy (¹H-MRS) has been used to provide useful information about the neurochemical changes reflecting early pathological alterations in Alzheimer's disease (AD) brain. In this study, we have longitudinally measured the hippocampal neurochemical profile in vitro in senescent mice induced with chronic injection of D-Galactose and NaNO₂, at different time point from day 30 to day 70 with a 10-day interval. Pathological brain alterations induced by D-Galactose and NaNO₂ were monitored through hematoxylin and eosin (HE) staining, Congo red staining and bielschowsky silver staining, and the cognition deficits were assessed via Morris Water Maze (MWM) test. This D-galactose and NaNO₂ treated mouse model, characterized by an early-onset memory dysfunction, a robust neuronal loss, amyloid plaques and neurofibrillary tangles in hippocampal subdivision, well mimics a prodromal Alzheimer's phenotype. Consistent with previously published in vivo ¹H MRS findings in human AD patients and AD transgenic mice, our in vitro ¹H MRS on the perchloric acid extractions of hippocampus in senescent mice observed significant decreases of N-acetylaspartate (NAA) and Glutamate (Glu) but an increase in Myo-inositol (mIns). Elevated mIns occurred prior to the reduction of NAA and Glu during the progression of aging. In addition, changes in mIns, NAA and Glu were found to precede pathological abnormalities. Overall, our in vitro findings in senescent mice validated the concept that hippocampal neurochemical alternations preceded the pathological changes of the brain, and could serve as potential markers of AD progression. Reductions of NAA and Glu can be interpreted in terms of neuronal degeneration and dysfunctions in glutamatergic activity that may contribute to the pathophysiological mechanisms underlying AD. Elevated mIns might be related to glial activation. Further experiments are needed to explore the potential value of mIns in the early diagnosis of AD, to verify whether glial cell proliferation occurs earlier than neuronal changes.
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China ; Sichuan Provincial Tumor Hospital, Chengdu, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Yao
authors.affiliation: Shantou University Central Laboratory and NMR Unit, Shantou, Guangdong Province, China.
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.affiliation: Mental Health Center of Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Kezeng
authors.initials: K
authors.lastname: You
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China ; Key Laboratory of Molecular Imaging of Guangdong Province, Shantou, China.
authors.forename: Renhua
authors.initials: R
authors.lastname: Wu
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D001522:Behavior, Animal; D049109:Cell Proliferation; D003224:Congo Red / Q000737:chemistry; D018450:Disease Progression; D005690:Galactose / Q000737:chemistry*; D005973:Glutamine / Q000737:chemistry; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007294:Inositol / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D018782:Maze Learning; D051379:Mice; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012977:Sodium Nitrite / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000682:Amyloid; D005973:Glutamine; D001224:Aspartic Acid; D003224:Congo Red; D007294:Inositol; C000179:N-acetylaspartate; D012977:Sodium Nitrite; D005690:Galactose