PMID- 32279604
OWN - NLM
STAT- MEDLINE
DCOM- 20210914
LR  - 20211204
IS  - 1557-8577 (Electronic)
IS  - 1549-1684 (Linking)
VI  - 23
IP  - 6
DP  - 2020 Dec
TI  - 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.
PG  - 485-497
LID - 10.1089/rej.2019.2297 [doi]
AB  - 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.
FAU - Celebi-Birand, Dilan
AU  - Celebi-Birand D
AD  - Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research 
      Center, Bilkent University, Ankara, Turkey.
AD  - UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, 
      Ankara, Turkey.
AD  - Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, 
      Turkey.
FAU - Ardic, Narin Ilgim
AU  - Ardic NI
AD  - Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research 
      Center, Bilkent University, Ankara, Turkey.
AD  - UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, 
      Ankara, Turkey.
AD  - Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, 
      Turkey.
FAU - Karoglu-Eravsar, Elif Tugce
AU  - Karoglu-Eravsar ET
AD  - Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research 
      Center, Bilkent University, Ankara, Turkey.
AD  - UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, 
      Ankara, Turkey.
AD  - Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, 
      Turkey.
FAU - Sengul, Goksemin Fatma
AU  - Sengul GF
AD  - Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research 
      Center, Bilkent University, Ankara, Turkey.
AD  - UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, 
      Ankara, Turkey.
AD  - Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, 
      Turkey.
AD  - Department of Cellular Biochemistry, Universitatsmedizin Gottingen, Gottingen, 
      Germany.
FAU - Kafaligonul, Hulusi
AU  - Kafaligonul H
AD  - Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research 
      Center, Bilkent University, Ankara, Turkey.
AD  - Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, 
      Turkey.
AD  - National Magnetic Resonance Research Center (UMRAM), Bilkent University, Ankara, 
      Turkey.
FAU - Adams, Michelle M
AU  - Adams MM
AD  - Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research 
      Center, Bilkent University, Ankara, Turkey.
AD  - UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, 
      Ankara, Turkey.
AD  - Zebrafish Facility, Bilkent University Molecular Biology and Genetics, Ankara, 
      Turkey.
AD  - Department of Psychology, Bilkent University, Ankara, Turkey.
LA  - eng
PT  - Journal Article
DEP - 20200519
PL  - United States
TA  - Rejuvenation Res
JT  - Rejuvenation research
JID - 101213381
RN  - 0 (Biomarkers)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aging/*metabolism
MH  - Animals
MH  - Autophagy/drug effects
MH  - Biomarkers/metabolism
MH  - Brain/drug effects/*metabolism
MH  - Fasting/*metabolism
MH  - Female
MH  - Male
MH  - Neuroglia/drug effects/*metabolism
MH  - Neurons/*cytology/drug effects/metabolism
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Zebrafish/*metabolism
OTO - NOTNLM
OT  - aging
OT  - brain
OT  - intermittent fasting
OT  - mTOR signaling
OT  - rapamycin
OT  - zebrafish
EDAT- 2020/04/14 06:00
MHDA- 2021/09/15 06:00
CRDT- 2020/04/14 06:00
PHST- 2020/04/14 06:00 [pubmed]
PHST- 2021/09/15 06:00 [medline]
PHST- 2020/04/14 06:00 [entrez]
AID - 10.1089/rej.2019.2297 [doi]
PST - ppublish
SO  - Rejuvenation Res. 2020 Dec;23(6):485-497. doi: 10.1089/rej.2019.2297. Epub 2020 
      May 19.