| First Author | Chalkiadaki K | Year | 2023 |
| Journal | Front Cell Dev Biol | Volume | 11 |
| Pages | 1205112 | PubMed ID | 37293130 |
| Mgi Jnum | J:346335 | Mgi Id | MGI:7488808 |
| Doi | 10.3389/fcell.2023.1205112 | Citation | Chalkiadaki K, et al. (2023) Reversal of memory and autism-related phenotypes in Tsc2(+/-) mice via inhibition of Nlgn1. Front Cell Dev Biol 11:1205112 |
| abstractText | Tuberous sclerosis complex (TSC) is a rare monogenic disorder co-diagnosed with high rates of autism and is caused by loss of function mutations in the TSC1 or TSC2 genes. A key pathway hyperactivated in TSC is the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which regulates cap-dependent mRNA translation. We previously demonstrated that exaggerated cap-dependent translation leads to autism-related phenotypes and increased mRNA translation and protein expression of Neuroligin 1 (Nlgn1) in mice. Inhibition of Nlgn1 expression reversed social behavior deficits in mice with increased cap-dependent translation. Herein, we report elevated translation of Nlgn1 mRNA and an increase in its protein expression. Genetic or pharmacological inhibition of Nlgn1 expression in Tsc2 (+/-) mice rescued impaired hippocampal mGluR-LTD, contextual discrimination and social behavior deficits in Tsc2 (+/-) mice, without correcting mTORC1 hyperactivation. Thus, we demonstrate that reduction of Nlgn1 expression in Tsc2 (+/-) mice is a new therapeutic strategy for TSC and potentially other neurodevelopmental disorders. |
