PMID- 37052995
OWN - NLM
STAT- MEDLINE
DCOM- 20230424
LR  - 20230508
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 15
IP  - 7
DP  - 2023 Apr 12
TI  - Viral vector-mediated upregulation of serine racemase expression in medial 
      prefrontal cortex improves learning and synaptic function in middle age rats.
PG  - 2433-2449
LID - 10.18632/aging.204652 [doi]
AB  - An age-associated decrease in N-methyl-D-aspartate receptor (NMDAR)-mediated 
      synaptic function contributes to impaired synaptic plasticity and is associated 
      with cognitive impairments. Levels of serine racemase (SR), an enzyme that 
      synthesizes D-serine, an NMDAR co-agonist, decline with age. Thus, enhancing 
      NMDAR function via increased SR expression in middle age, when subtle declines in 
      cognition emerge, was predicted to enhance performance on a prefrontal 
      cortex-mediated task sensitive to aging. Middle-aged (~12 mo) male Fischer-344 
      rats were injected bilaterally in the medial prefrontal cortex (mPFC) with viral 
      vector (LV), SR (LV-SR) or control (LV-GFP). Rats were trained on the operant 
      attentional set-shift task (AST) to examine cognitive flexibility and attentional 
      function. LV-SR rats exhibited a faster rate of learning compared to controls 
      during visual discrimination of the AST. Extradimensional set shifting and 
      reversal were not impacted. Immunohistochemical analyses demonstrated that LV-SR 
      significantly increased SR expression in the mPFC. Electrophysiological 
      characterization of synaptic transmission in the mPFC slices obtained from LV-GFP 
      and LV-SR animals indicated a significant increase in isolated NMDAR-mediated 
      synaptic responses in LV-SR slices. Thus, results of the current study 
      demonstrated that prefrontal SR upregulation in middle age rats can improve 
      learning of task contingencies for visual discrimination and increase 
      glutamatergic synaptic transmission, including NMDAR activity.
FAU - Yegla, Brittney
AU  - Yegla B
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL 32611, USA.
FAU - Rani, Asha
AU  - Rani A
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL 32611, USA.
FAU - Kumar, Ashok
AU  - Kumar A
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL 32611, USA.
LA  - eng
GR  - R01 AG037984/AG/NIA NIH HHS/United States
GR  - R21 AG068205/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230412
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - EC 5.1.1.16 (serine racemase)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Male
MH  - Up-Regulation
MH  - *Prefrontal Cortex/physiology
MH  - *Synaptic Transmission
MH  - Rats, Inbred F344
PMC - PMC10120901
OTO - NOTNLM
OT  - D-serine
OT  - NMDA receptor
OT  - aging
OT  - cognitive flexibility
OT  - medial prefrontal cortex
OT  - serine racemase
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to 
      this study. Brittney Yegla currently works at Supernus Pharmaceuticals, though 
      the company did not sponsor or support this work.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/24 06:42
PMCR- 2023/04/15
CRDT- 2023/04/13 11:53
PHST- 2023/01/19 00:00 [received]
PHST- 2023/04/03 00:00 [accepted]
PHST- 2023/04/24 06:42 [medline]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/04/13 11:53 [entrez]
PHST- 2023/04/15 00:00 [pmc-release]
AID - 204652 [pii]
AID - 10.18632/aging.204652 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2023 Apr 12;15(7):2433-2449. doi: 10.18632/aging.204652. Epub 
      2023 Apr 12.