PMID- 33023260
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20210226
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 19
DP  - 2020 Oct 2
TI  - Adenosine Metabolism in the Cerebral Cortex from Several Mice Models during 
      Aging.
LID - 10.3390/ijms21197300 [doi]
LID - 7300
AB  - Adenosine is a neuromodulator that has been involved in aging and 
      neurodegenerative diseases as Alzheimer's disease (AD). In the present work, we 
      analyzed the possible modulation of purine metabolites, 5'nucleotidase (5'NT) and 
      adenosine deaminase (ADA) activities, and adenosine monophosphate (AMP)-activated 
      protein kinase (AMPK) and its phosphorylated form during aging in the cerebral 
      cortex. Three murine models were used: senescence-accelerated mouse-resistant 1 
      (SAMR1, normal senescence), senescence-accelerated mouse-prone 8 (SAMP8, a model 
      of AD), and the wild-type C57BL/6J (model of aging) mice strains. Glutamate and 
      excitatory amino acid transporter 2 (EAAT2) levels were also measured in these 
      animals. HPLC, Western blotting, and enzymatic activity evaluation were performed 
      to this aim. 5'-Nucleotidase (5'NT) activity was decreased at six months and 
      recovered at 12 months in SAMP8 while opposite effects were observed in SAMR1 at 
      the same age, and no changes in C57BL/6J mice. ADA activity significantly 
      decreased from 3 to 12 months in the SAMR1 mice strain, while a significant 
      decrease from 6 to 12 months was observed in the SAMP8 mice strain. Regarding 
      purine metabolites, xanthine and guanosine levels were increased at six months in 
      SAMR1 without significant differences in SAMP8 mice. In C57BL/6J mice, inosine 
      and xanthine were increased, while adenosine decreased, from 4 to 24 months. The 
      AMPK level was decreased at six months in SAMP8 without significant changes nor 
      in SAMR1 or C57BL/6J strains. Glutamate and EAAT2 levels were also modulated 
      during aging. Our data show a different modulation of adenosine metabolism 
      participants in the cerebral cortex of these animal models. Interestingly, the 
      main differences between SAMR1 and SAMP8 mice were found at six months of age, 
      SAMP8 being the most affected strain. As SAMP8 is an AD model, results suggest 
      that adenosinergic metabolism is involved in the neurodegeneration of AD.
FAU - Sanchez-Melgar, Alejandro
AU  - Sanchez-Melgar A
AD  - Universidad de Castilla-La Mancha, Department of Inorganic, Organic and 
      Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine 
      of Ciudad Real, Regional Center of Biomedical Research (CRIB), 13071 Ciudad Real, 
      Spain.
FAU - Albasanz, Jose Luis
AU  - Albasanz JL
AUID- ORCID: 0000-0002-9927-5076
AD  - Universidad de Castilla-La Mancha, Department of Inorganic, Organic and 
      Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine 
      of Ciudad Real, Regional Center of Biomedical Research (CRIB), 13071 Ciudad Real, 
      Spain.
FAU - Pallas, Merce
AU  - Pallas M
AUID- ORCID: 0000-0003-3095-4254
AD  - Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy and 
      Food Sciences, Institute of Neuroscience, University of Barcelona, 08028 
      Barcelona, Spain.
FAU - Martin, Mairena
AU  - Martin M
AD  - Universidad de Castilla-La Mancha, Department of Inorganic, Organic and 
      Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine 
      of Ciudad Real, Regional Center of Biomedical Research (CRIB), 13071 Ciudad Real, 
      Spain.
LA  - eng
GR  - PID2019-109206GB-I00/Ministerio de Ciencia, Innovacion y Universidades/
GR  - SAF2016-33307/Ministerio de Ciencia, Innovacion y Universidades/
GR  - SBPLY/19/180501/000251/Junta de Comunidades de Castilla-La Mancha/
GR  - 2020-GRIN-29108/Universidad de Castilla-La Mancha/
GR  - PRE-8002/2014/Junta de Comunidades de Castilla-La Mancha/
PT  - Journal Article
DEP - 20201002
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 1AVZ07U9S7 (Xanthine)
RN  - 5A614L51CT (Inosine)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*metabolism
MH  - Aging/genetics/*metabolism/pathology
MH  - Alzheimer Disease/*genetics/metabolism/pathology
MH  - Animals
MH  - Cellular Senescence/genetics
MH  - Cerebral Cortex/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Hippocampus/metabolism/pathology
MH  - Humans
MH  - Inosine/metabolism
MH  - Mice
MH  - Phosphorylation/genetics
MH  - Xanthine/metabolism
PMC - PMC7582336
OTO - NOTNLM
OT  - adenosine metabolism
OT  - aging
OT  - animal models
OT  - glutamate
OT  - purinergic signaling
COIS- The authors declare no conflict of interest. The sponsors had no role in the 
      design, execution, interpretation, or writing of the study.
EDAT- 2020/10/08 06:00
MHDA- 2021/02/27 06:00
PMCR- 2020/10/01
CRDT- 2020/10/07 01:02
PHST- 2020/07/26 00:00 [received]
PHST- 2020/09/27 00:00 [revised]
PHST- 2020/10/01 00:00 [accepted]
PHST- 2020/10/07 01:02 [entrez]
PHST- 2020/10/08 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2020/10/01 00:00 [pmc-release]
AID - ijms21197300 [pii]
AID - ijms-21-07300 [pii]
AID - 10.3390/ijms21197300 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Oct 2;21(19):7300. doi: 10.3390/ijms21197300.