PMID- 28733898
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20190215
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 55
IP  - 6
DP  - 2018 Jun
TI  - (D)-Cycloserine Ameliorates Autism-Like Deficits by Removing GluA2-Containing 
      AMPA Receptors in a Valproic Acid-Induced Rat Model.
PG  - 4811-4824
LID - 10.1007/s12035-017-0685-1 [doi]
AB  - Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum 
      disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor 
      (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the 
      amygdala. NMDAR partial agonist (D)-cycloserine (DCS) has been reported to act as 
      a cognitive enhancer by increasing the NMDAR response to improve autistic-like 
      phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is 
      still unknown. Using combined behavioral, electrophysiological, and molecular 
      approaches, we found that DCS administration rescued social interaction deficits 
      and anxiety/repetitive-like behaviors observed in VPA-exposed offspring. In the 
      amygdala synapses, DCS treatment reversed the decreased paired pulse ratio (PPR) 
      and the impaired NMDAR-dependent LTD, increased the frequency and amplitude of 
      miniature excitatory post-synaptic currents (mEPSCs), and resulted in a higher 
      dendritic spine density at the amygdala synapses in the VPA-exposed offspring. 
      Moreover, we found that DCS facilitated the removal of GluA2-containing 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (GluA2/AMPARs) by 
      inducing NMDAR-dependent LTD in the VPA-exposed offspring. We further established 
      that the effects of DCS treatment, including increased GluA2/AMPAR removal and 
      rescues of impaired social behavior, were blocked by Tat-GluA2(3Y), a 
      GluA2-derived peptide that disrupted regulation of AMPAR endocytosis. These 
      results provided the first evidence that rescue of the ASD-like phenotype by DCS 
      is mediated by the mechanism of GluA2/AMPAR removal in VPA-exposed rat offspring.
FAU - Wu, Han-Fang
AU  - Wu HF
AD  - Department and Institute of Physiology, School of Medicine, National Yang-Ming 
      University, Taipei, 11221, Taiwan.
FAU - Chen, Po See
AU  - Chen PS
AD  - Department of Psychiatry, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
AD  - Addiction Research Center, National Cheng Kung University, Tainan, 70101, Taiwan.
FAU - Hsu, Ya-Ting
AU  - Hsu YT
AD  - Department and Institute of Physiology, School of Medicine, National Yang-Ming 
      University, Taipei, 11221, Taiwan.
FAU - Lee, Chi-Wei
AU  - Lee CW
AD  - Department and Institute of Physiology, School of Medicine, National Yang-Ming 
      University, Taipei, 11221, Taiwan.
FAU - Wang, Tzu-Feng
AU  - Wang TF
AD  - Department of Psychiatry, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
AD  - Taiwan International Graduate Program in Interdisciplinary Neuroscience, National 
      Cheng Kung University and Academia Sinica, Taipei, Taiwan.
FAU - Chen, Yi-Ju
AU  - Chen YJ
AD  - Department and Institute of Physiology, School of Medicine, National Yang-Ming 
      University, Taipei, 11221, Taiwan.
FAU - Lin, Hui-Ching
AU  - Lin HC
AUID- ORCID: 0000-0002-1639-9293
AD  - Department and Institute of Physiology, School of Medicine, National Yang-Ming 
      University, Taipei, 11221, Taiwan. hclin7@ym.edu.tw.
AD  - Brain Research Center, National Yang-Ming University, Taipei, 11221, Taiwan. 
      hclin7@ym.edu.tw.
AD  - Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and 
      Technology, Taipei Medical University, Taipei, 11031, Taiwan. hclin7@ym.edu.tw.
LA  - eng
GR  - MOST 105-2628-B-010-006-MY3/Ministry of Science Research and Technology (R.O.C)/
GR  - MOST 103-2321-B-010-016/Ministry of Science Research and Technology (R.O.C)/
GR  - MOST 104-2314-B-006-030-MY3/Ministry of Science and Technology (R.O.C)/
GR  - MOST 99-2628-B-006-013-MY3/Ministry of Science and Technology (R.O.C)/
GR  - CI-105-12/YEN TJING LING MEDICAL FUNDATION,Taiwan/
GR  - #NYMU-FEMH 106DN09/National Yang-Ming University-Far Eastern Memorial Hospital 
      Joint Research Program/
PT  - Journal Article
DEP - 20170721
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Receptors, AMPA)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - 95IK5KI84Z (Cycloserine)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Amygdala/*drug effects/metabolism
MH  - Animals
MH  - Autism Spectrum Disorder/chemically induced/*drug therapy/metabolism
MH  - Behavior, Animal/*drug effects
MH  - Cycloserine/pharmacology/*therapeutic use
MH  - Disease Models, Animal
MH  - Male
MH  - Motor Activity/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/*metabolism
MH  - *Social Behavior
MH  - Synapses/metabolism
MH  - Valproic Acid
OTO - NOTNLM
OT  - Autism spectrum disorder
OT  - D-Cycloserine
OT  - GluA2/AMPARs
OT  - Long-term depression
OT  - NMDARs
OT  - Valproic acid
EDAT- 2017/07/25 06:00
MHDA- 2019/02/12 06:00
CRDT- 2017/07/23 06:00
PHST- 2017/04/19 00:00 [received]
PHST- 2017/07/10 00:00 [accepted]
PHST- 2017/07/25 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2017/07/23 06:00 [entrez]
AID - 10.1007/s12035-017-0685-1 [pii]
AID - 10.1007/s12035-017-0685-1 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2018 Jun;55(6):4811-4824. doi: 10.1007/s12035-017-0685-1. Epub 
      2017 Jul 21.