Metabolic changes in rat brain following intracerebroventricular injections of streptozotocin: A model of sporadic Alzheimer’s disease
Abstract
A decrease in cerebral glucose metabolic uptake is an early and characteristic sign of Alzheimer's disease (AD). Streptozotocin (STZ) is a bacterial toxin which damages insulin-producing cells and insulin receptors. Intracerebroventricular (icv) application of STZ in rats has been found to chronically decrease cerebral glucose uptake and produce other effects that bear a resemblance to several other molecular and pathological features of AD. In the present experiments in vivo (1)H MR Spectroscopy with short echo time (3 ms) was used to non-invasively obtain a neurochemical profile of rat brains, 3 weeks and 2 months after double icv injections of STZ or vehicle. Seventeen metabolites were quantified from 27 microL tissue volume which included hippocampus and a part of cerebral cortex, using the LCModel and unsuppressed water signal as an internal reference. Three weeks after icv STZ several metabolites were significantly decreased, the most prominent changes noted in glycerophosphocholine and phosphocholine (-38 +/- 5%), glutathione (-37 +/- 4%), taurine (-30 +/- 19%), glutamate (-26 +/- 14%), phosphocreatine (-23 +/- 15%) and N-acetylaspartate (-16 +/- 6%). On the contrary, the concentration of N-acetylaspartylglutamate was found significantly increased (+38 +/- 18%). After 2 months some of these changes were even more pronounced. We conclude that in vivo (1)H MRS of rat brain following icv STZ injections provides a new input into a better understanding of the critical dependency of neural function and structure on brain glucose consumption, and may be of relevance in further studies of AD pathomechanism.
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AD-like changes have been observed in experimental models of insulin resistance, including animals fed a high fat diet or receiving intracerebral or IP injections of streptozotocin.
“Supporting this idea, AD-like changes have been observed in experimental models of insulin resistance, including animals fed a high fat diet or receiving intracerebral or IP injections of streptozotocin (Cao et al., 2007; Labak et al., 2010; Lester-Coll et al., 2006; Ma et al., 2009; Pratchayasakul et al., 2011; Tong et al., 2009; Zhang et al., 2009).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Labak et al., 2010
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- Authors
- Labak, M., Foniok, T., Kirk, D., Rushforth, D., Tomanek, B., Jasiński, A., & Grieb, P.
- Affiliations
- Institute of Nuclear Physics, Polish Academy of Sciences (PL)
- National Research Council Canada (CA)
- Mossakowski Medical Research Institute, Polish Academy of Sciences (PL)
- Corresponding author
- Grieb, P.
- Venue
- Acta neurochirurgica. Supplementum
- Publisher
- Springer Vienna
- Published
- 2009-08-31
- Volume
- 106
- Pages
- 177-181
- ISSN
- 0065-1419 (ISSN-L)
- OpenAlex
- W120784412
- Cited by
- 79
- References
- 19
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 4
- FWCI
- 13.10
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta neurochirurgica. Supplementum (publishedVersion)
- PubMed (publishedVersion)
- NPARC (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- Alzheimer's disease, streptozotocin, intracerebroventricular administration, brain metabolites, brain glucose metabolism, N-acetylaspartate, N-acetylaspartylglutamate, glutathione, phosphocreatine, glycerophosphocholine, taurine, glutamate, hippocampus, cerebral cortex, animal models of Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Amino Acids, Animals, Aspartic Acid, Brain, Brain Chemistry, Disease Models, Animal, Electrons, Glucose, Glutathione, Injections, Intraventricular, Magnetic Resonance Imaging, Male, Magnetic Resonance Spectroscopy, Streptozocin, Rats, Wistar, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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