SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome.

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

SUBMITTER: Yamaguchi K 

PROVIDER: S-EPMC6163584 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature