PMID- 30231518
OWN - NLM
STAT- MEDLINE
DCOM- 20190121
LR  - 20231213
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 9
DP  - 2018 Sep 18
TI  - SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and 
      Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome.
LID - 10.3390/ijms19092811 [doi]
LID - 2811
AB  - alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by 
      mutations in ATRX. An ATR-X model mouse lacking Atrx exon 2 displays phenotypes 
      that resemble symptoms in the human intellectual disability: cognitive defects 
      and abnormal dendritic spine formation. We herein target activation of sigma-1 
      receptor (Sig-1R) that can induce potent neuroprotective and neuroregenerative 
      effects by promoting the activity of neurotrophic factors, such as brain-derived 
      neurotrophic factor (BDNF). We demonstrated that treatment with SA4503, a potent 
      activator of Sig-1R, reverses axonal development and dendritic spine 
      abnormalities in cultured cortical neurons from ATR-X model mice. Moreover, the 
      SA4503 treatment rescued cognitive deficits exhibited by the ATR-X model mice. We 
      further found that significant decreases in the BDNF-protein level in the medial 
      prefrontal cortex of ATR-X model mice were recovered with treatment of SA4503. 
      These results indicate that the rescue of dendritic spine abnormalities through 
      the activation of Sig-1R has a potential for post-diagnostic therapy in ATR-X 
      syndrome.
FAU - Yamaguchi, Kouya
AU  - Yamaguchi K
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai 980-8578, Japan. kouya.yamaguchi.r3@dc.tohoku.ac.jp.
FAU - Shioda, Norifumi
AU  - Shioda N
AD  - Department of Genomic Neurology, Institute of Molecular Embryology and Genetics, 
      Kumamoto University, Kumamoto 860-0811, Japan. shioda@kumamoto-u.ac.jp.
FAU - Yabuki, Yasushi
AU  - Yabuki Y
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai 980-8578, Japan. yabukiy@m.tohoku.ac.jp.
FAU - Zhang, Chen
AU  - Zhang C
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 31005, 
      Zhejiang, China. chenzhang@zju.edu.cn.
FAU - Han, Feng
AU  - Han F
AD  - School of Pharmacy, Nanjing Medical University, Nanjing 211166, Jiangsu, China. 
      fenghan169@njmu.edu.cn.
FAU - Fukunaga, Kohji
AU  - Fukunaga K
AUID- ORCID: 0000-0001-8526-2824
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai 980-8578, Japan. kfukunaga@m.tohoku.ac.jp.
LA  - eng
GR  - 24659024/MEXT/JSPS KAKENHI/
GR  - 25110705/MEXT/JSPS KAKENHI/
PT  - Journal Article
DEP - 20180918
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ligands)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Piperazines)
RN  - 0 (Receptors, sigma)
RN  - 9J7A4144BX (SA 4503)
RN  - ATR-X syndrome
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cells, Cultured
MH  - Cognitive Dysfunction/*drug therapy/etiology/physiopathology
MH  - Disease Models, Animal
MH  - Ligands
MH  - Male
MH  - Mental Retardation, X-Linked/complications/*drug therapy/physiopathology
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*therapeutic use
MH  - Piperazines/*therapeutic use
MH  - Receptors, sigma/*metabolism
MH  - alpha-Thalassemia/complications/*drug therapy/physiopathology
MH  - Sigma-1 Receptor
PMC - PMC6163584
OTO - NOTNLM
OT  - ATR-X syndrome
OT  - brain-derived neurotrophic factor
OT  - cognitive function
OT  - dendritic spine
OT  - sigma-1 receptor
COIS- The authors declare no conflict of interest.
EDAT- 2018/09/21 06:00
MHDA- 2019/01/22 06:00
PMCR- 2018/09/01
CRDT- 2018/09/21 06:00
PHST- 2018/07/31 00:00 [received]
PHST- 2018/09/10 00:00 [revised]
PHST- 2018/09/12 00:00 [accepted]
PHST- 2018/09/21 06:00 [entrez]
PHST- 2018/09/21 06:00 [pubmed]
PHST- 2019/01/22 06:00 [medline]
PHST- 2018/09/01 00:00 [pmc-release]
AID - ijms19092811 [pii]
AID - ijms-19-02811 [pii]
AID - 10.3390/ijms19092811 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Sep 18;19(9):2811. doi: 10.3390/ijms19092811.