PMID- 31339863
OWN - NLM
STAT- MEDLINE
DCOM- 20200609
LR  - 20240216
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 11
IP  - 14
DP  - 2019 Jul 24
TI  - Subunit contribution to NMDA receptor hypofunction and redox sensitivity of 
      hippocampal synaptic transmission during aging.
PG  - 5140-5157
LID - 10.18632/aging.102108 [doi]
AB  - We examined the contribution of N-methyl-D-aspartate receptor (NMDAR) subunits in 
      the redox-mediated decline in NMDAR function during aging. GluN2A and GluN2B 
      selective antagonists decreased peak NMDAR currents to a similar extent in young 
      and aged animals, indicating that a shift in diheteromeric GluN2 subunits does 
      not underlie the age-related decrease in the NMDAR synaptic function. Application 
      of dithiothreitol (DTT) in aged animals, increased peak NMDAR synaptic currents, 
      prolonged the decay time, and increased the sensitivity of the synaptic response 
      to the GluN2B antagonist, ifenprodil, indicating that DTT increased the 
      contribution of GluN2B subunits to the synaptic response. The DTT-mediated 
      increase in NMDAR function was inhibited by partial blockade of NMDARs, and this 
      inhibition was rescued by increasing Ca(2+) concentration in the recording 
      medium. The results indicate that DTT-mediated potentiation requires Ca(2+) 
      influx through NMDAR activity. Finally, redox regulation of NMDAR function 
      depends on the activity of Ca(2+)/calmodulin-dependent protein kinase II 
      (CaMKII). The results indicate that activity-dependent NMDAR synaptic plasticity 
      is suppressed by redox-mediated inhibition of CaMKII activation during aging. The 
      redox regulation of NMDARs represents a suppression of a metaplasticity 
      mechanism, which can disrupt synaptic plasticity and cognition associated with 
      neurological or psychiatric diseases, and aging.
FAU - Kumar, Ashok
AU  - Kumar A
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL 32611, USA.
FAU - Thinschmidt, Jeffrey S
AU  - Thinschmidt JS
AD  - Department of Pharmacology and Therapeutics, University of Florida, Gainesville, 
      FL 32611, USA.
FAU - Foster, Thomas C
AU  - Foster TC
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL 32611, USA.
AD  - Genetics and Genomics Program, University of Florida, Gainesville, FL 32611, USA.
LA  - eng
GR  - R01 AG052258/AG/NIA NIH HHS/United States
GR  - R37 AG036800/AG/NIA NIH HHS/United States
GR  - P30 AG028740/AG/NIA NIH HHS/United States
GR  - R01 AG049711/AG/NIA NIH HHS/United States
GR  - R01 AG037984/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Oxidants)
RN  - 0 (Piperidines)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - R8OE3P6O5S (ifenprodil)
RN  - T8ID5YZU6Y (Dithiothreitol)
RN  - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A)
SB  - IM
MH  - *Aging
MH  - Animals
MH  - CA1 Region, Hippocampal/cytology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Dithiothreitol/pharmacology
MH  - Male
MH  - Models, Animal
MH  - *Neuronal Plasticity
MH  - Oxidants/pharmacology
MH  - Oxidation-Reduction
MH  - Piperidines/pharmacology
MH  - Protein Subunits/antagonists & inhibitors/metabolism
MH  - Pyramidal Cells/*metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - *Synaptic Transmission
PMC - PMC6682512
OTO - NOTNLM
OT  - CA1 pyramidal neurons
OT  - NMDA receptor current
OT  - aging
OT  - dithiothreitol
OT  - hippocampus
OT  - redox state
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2019/07/25 06:00
MHDA- 2020/06/10 06:00
PMCR- 2019/07/31
CRDT- 2019/07/25 06:00
PHST- 2019/06/03 00:00 [received]
PHST- 2019/07/14 00:00 [accepted]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/06/10 06:00 [medline]
PHST- 2019/07/25 06:00 [entrez]
PHST- 2019/07/31 00:00 [pmc-release]
AID - 102108 [pii]
AID - 10.18632/aging.102108 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2019 Jul 24;11(14):5140-5157. doi: 10.18632/aging.102108.