| RRC ID |
88300
|
| Author |
Yamaguchi K, Shioda N, Yabuki Y, Zhang C, Han F, Fukunaga K.
|
| Title |
SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome.
|
| Journal |
Int J Mol Sci
|
| Abstract |
α-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.
|
| Volume |
19(9)
|
| Published |
2018-9-18
|
| DOI |
10.3390/ijms19092811
|
| PII |
ijms19092811
|
| PMID |
30231518
|
| PMC |
PMC6163584
|
| MeSH |
Animals
Brain-Derived Neurotrophic Factor / metabolism
Cells, Cultured
Cognitive Dysfunction / drug therapy*
Cognitive Dysfunction / etiology
Cognitive Dysfunction / physiopathology
Disease Models, Animal
Ligands
Male
Mice, Inbred C57BL
Neuroprotective Agents / therapeutic use*
Piperazines / therapeutic use*
Receptors, sigma / metabolism*
Sigma-1 Receptor
X-Linked Intellectual Disability / complications
X-Linked Intellectual Disability / drug therapy*
X-Linked Intellectual Disability / physiopathology
alpha-Thalassemia / complications
alpha-Thalassemia / drug therapy*
alpha-Thalassemia / physiopathology
|
| IF |
4.556
|
| Resource |
| Mice |
RBRC04937 |
