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Tytuł pozycji:

Dietary and Pharmacological Interventions That Inhibit Mammalian Target of Rapamycin Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in an Age-and Treatment-Dependent Manner.

Tytuł:
Dietary and Pharmacological Interventions That Inhibit Mammalian Target of Rapamycin Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in an Age-and Treatment-Dependent Manner.
Autorzy:
Celebi-Birand D; Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey.; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.; Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, Turkey.
Ardic NI; Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey.; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.; Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, Turkey.
Karoglu-Eravsar ET; Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey.; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.; Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, Turkey.
Sengul GF; Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey.; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.; Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, Turkey.; Department of Cellular Biochemistry, Universitätsmedizin Göttingen, Göttingen, Germany.
Kafaligonul H; Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey.; Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, Turkey.; National Magnetic Resonance Research Center (UMRAM), Bilkent University, Ankara, Turkey.
Adams MM; Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey.; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.; Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, Turkey.; Department of Psychology, Bilkent University, Ankara, Turkey.
Źródło:
Rejuvenation research [Rejuvenation Res] 2020 Dec; Vol. 23 (6), pp. 485-497. Date of Electronic Publication: 2020 May 19.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Larchmont, NY : Mary Ann Liebert Inc., c2004-
MeSH Terms:
Aging/*metabolism
Brain/*metabolism
Fasting/*metabolism
Neuroglia/*metabolism
Neurons/*cytology
Sirolimus/*pharmacology
TOR Serine-Threonine Kinases/*antagonists & inhibitors
Zebrafish/*metabolism
Animals ; Autophagy/drug effects ; Biomarkers/metabolism ; Brain/drug effects ; Female ; Male ; Neuroglia/drug effects ; Neurons/drug effects ; Neurons/metabolism ; TOR Serine-Threonine Kinases/metabolism
Contributed Indexing:
Keywords: aging; brain; intermittent fasting; mTOR signaling; rapamycin; zebrafish
Substance Nomenclature:
0 (Biomarkers)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
W36ZG6FT64 (Sirolimus)
Entry Date(s):
Date Created: 20200414 Date Completed: 20210914 Latest Revision: 20211204
Update Code:
20240105
DOI:
10.1089/rej.2019.2297
PMID:
32279604
Czasopismo naukowe
Intermittent fasting (IF) and its mimetic, rapamycin extend lifespan and healthspan through mechanisms that are not fully understood. We investigated different short-term durations of IF and rapamycin on cellular and molecular changes in the brains of young (6-10 months) and old (26-31 months) zebrafish. Interestingly, our results showed that IF significantly lowered glucose levels while increasing DCAMKL1 in both young and old animals. This proliferative effect of IF was supported by the upregulation of foxm1 transcript in old animals. Rapamycin did not change glucose levels in young and old animals but had differential effects depending on age. In young zebrafish, proliferating cell nuclear antigen and the LC3-II/LC3-I ratio was decreased, whereas glial fibrillary acidic protein and gephyrin were decreased in old animals. The changes in proliferative markers and a marker of autophagic flux suggest an age-dependent interplay between autophagy and cell proliferation. Additionally, changes in glia and inhibitory tone suggest a suppressive effect on neuroinflammation but may push the brain toward a more excitable state. Mammalian target of rapamycin (mTOR) activity in the brain following the IF and rapamycin treatment was differentially regulated by age. Interestingly, rapamycin inhibited mTOR more potently in young animals than IF. Principal component analysis supported our conclusion that the regulatory effects of IF and rapamycin were age-specific, since we observed different patterns in the expression levels and clustering of young and old animals. Taken together, our results suggest that even a short-term duration of IF and rapamycin have significant effects in the brain at young and old ages, and that these are age and treatment dependent.

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