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Csf Amino Acid Profiles in Icv-Streptozotocin-Induced Sporadic Alzheimer's Disease in Male Wistar Rat: A Metabolomics and Systems Biology Perspective Publisher Pubmed



Barzegar Behrooz A1, 2 ; Latifinavid H1, 3, 4 ; Lotfi J5 ; Khodagholi F6 ; Shojaei S2 ; Ghavami S2, 7, 8, 9 ; Fahanik Babaei J1
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Authors Affiliations
  1. 1. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Iran
  2. 2. Department of Human Anatomy and Cell Science, College of Medicine, University of Manitoba, Winnipeg, Canada
  3. 3. Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  4. 4. School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
  5. 5. Growth and Development Research Center, Tehran University of Medical Sciences, Iran
  6. 6. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Faculty of Medicine in Zabrze, University of Technology in Katowice, Zabrze, Poland
  8. 8. Research Institute of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, Canada
  9. 9. Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada

Source: FEBS Open Bio Published:2024


Abstract

Alzheimer's disease (AD) is an increasingly important public health concern due to the increasing proportion of older individuals within the general population. The impairment of processes responsible for adequate brain energy supply primarily determines the early features of the aging process. Restricting brain energy supply results in brain hypometabolism prior to clinical symptoms and is anatomically and functionally associated with cognitive impairment. The present study investigated changes in metabolic profiles induced by intracerebroventricular-streptozotocin (ICV-STZ) in an AD-like animal model. To this end, male Wistar rats received a single injection of STZ (3 mg·kg−1) by ICV (2.5 μL into each ventricle for 5 min on each side). In the second week after receiving ICV-STZ, rats were tested for cognitive performance using the Morris Water Maze test and subsequently prepared for positron emission tomography (PET) to confirm AD-like symptoms. Tandem Mass Spectrometry (MS/MS) analysis was used to detect amino acid changes in cerebrospinal fluid (CFS) samples. Our metabolomics study revealed a reduction in the concentrations of various amino acids (alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine) in CSF of ICV-STZ-treated animals as compared to controls rats. The results of the current study indicate amino acid levels could potentially be considered targets of nutritional and/or pharmacological interventions to interfere with AD progression. © 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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