PMID- 37453994
OWN - NLM
STAT- MEDLINE
DCOM- 20230928
LR  - 20230930
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 60
IP  - 11
DP  - 2023 Nov
TI  - Improvement of Learning and Memory by Elevating Brain D-Aspartate in a Mouse 
      Model of Fragile X Syndrome.
PG  - 6410-6423
LID - 10.1007/s12035-023-03438-0 [doi]
AB  - Fragile X syndrome (FXS) is an inherited human mental retardation that arises 
      from expansion of a CGG repeat in the Fmr1 gene, causing loss of the fragile X 
      mental retardation protein (FMRP). It is reported that N-methyl-D-aspartate 
      receptor (NMDAR)-mediated facilitation of long-term potentiation (LTP) and fear 
      memory are impaired in Fmr1 knockout (KO) mice. In this study, biological, 
      pharmacological, and electrophysiological techniques were performed to determine 
      the roles of D-aspartate (D-Asp), a modulator of NMDAR, and its metabolizing 
      enzyme D-aspartate oxidase (DDO) in Fmr1 KO mice. Levels of D-Asp were decreased 
      in the medial prefrontal cortex (mPFC ); however, the levels of its metabolizing 
      enzyme DDO were increased. Electrophysiological recordings indicated that oral 
      drinking of D-Asp recovered LTP induction in mPFC from Fmr1 KO mice. Moreover, 
      chronic oral administration of D-Asp reversed behavioral deficits of cognition 
      and locomotor coordination in Fmr1 KO mice. The therapeutic action of D-Asp was 
      partially through regulating functions of NMDARs and mGluR5/mTOR/4E-BP signaling 
      pathways. In conclusion, supplement of D-Asp may benefit for synaptic plasticity 
      and behaviors in Fmr1 KO mice and offer a potential therapeutic strategy for FXS.
CI  - (c) 2023. The Author(s).
FAU - Li, Yu-Jiao
AU  - Li YJ
AD  - Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, 710038, Shaanxi Province, China.
AD  - Department of Pharmacy, General Hospital of Eastern Theater Command/Jinling 
      Hospital, Medical School of Nanjing University, Nanjing, 210002, China.
FAU - Zhang, Kun
AU  - Zhang K
AD  - Department of Pharmacology, School of Pharmacy, Fourth Military Medical 
      University, Xi'an, 710032, Shaanxi Province, China.
FAU - Sun, Ting
AU  - Sun T
AD  - Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, 710038, Shaanxi Province, China.
FAU - Guo, Yan-Yan
AU  - Guo YY
AD  - Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, 710038, Shaanxi Province, China.
FAU - Yang, Qi
AU  - Yang Q
AD  - Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, 710038, Shaanxi Province, China.
FAU - Liu, Shui-Bing
AU  - Liu SB
AD  - Department of Pharmacology, School of Pharmacy, Fourth Military Medical 
      University, Xi'an, 710032, Shaanxi Province, China.
FAU - Wu, Yu-Mei
AU  - Wu YM
AD  - Department of Pharmacology, School of Pharmacy, Fourth Military Medical 
      University, Xi'an, 710032, Shaanxi Province, China. yumeiwu@fmmu.edu.cn.
FAU - Zhao, Ming-Gao
AU  - Zhao MG
AUID- ORCID: 0000-0002-7539-3887
AD  - Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, 710038, Shaanxi Province, China. minggao@fmmu.edu.cn.
LA  - eng
GR  - 31972902/National Natural Science Foundation of China/
GR  - 32241007/National Natural Science Foundation of China/
GR  - 82221001/National Natural Science Foundation of China/
GR  - 82071515/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230715
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 4SR0Q8YD1X (D-Aspartic Acid)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
RN  - 0 (Fmr1 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - *D-Aspartic Acid
MH  - *Fragile X Syndrome/drug therapy/metabolism
MH  - Learning
MH  - Long-Term Potentiation/physiology
MH  - Fragile X Mental Retardation Protein/metabolism
MH  - Mice, Knockout
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - Mice, Inbred C57BL
PMC - PMC10533629
OTO - NOTNLM
OT  - D-Aspartate
OT  - Fear memory
OT  - Fragile X syndrome
OT  - Long-term potentiation
OT  - mGluR5
COIS- The authors declare no competing interests.
EDAT- 2023/07/16 01:06
MHDA- 2023/09/28 06:42
PMCR- 2023/07/15
CRDT- 2023/07/15 23:05
PHST- 2023/03/19 00:00 [received]
PHST- 2023/06/10 00:00 [accepted]
PHST- 2023/09/28 06:42 [medline]
PHST- 2023/07/16 01:06 [pubmed]
PHST- 2023/07/15 23:05 [entrez]
PHST- 2023/07/15 00:00 [pmc-release]
AID - 10.1007/s12035-023-03438-0 [pii]
AID - 3438 [pii]
AID - 10.1007/s12035-023-03438-0 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2023 Nov;60(11):6410-6423. doi: 10.1007/s12035-023-03438-0. Epub 
      2023 Jul 15.