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MYT1L is an autism spectrum disorder (ASD)-associated transcription factor that is expressed in virtually all neurons throughout life. How MYT1L mutations cause neurological phenotypes and whether they can be targeted remains enigmatic. Here, we examine the effects of MYT1L deficiency in human neurons and mice. Mutant mice exhibit neurodevelopmental delays with thinner cortices, behavioural phenotypes, and gene expression changes that resemble those of ASD patients. MYT1L target genes, including WNT and NOTCH, are activated upon MYT1L depletion and their chemical inhibition can rescue delayed neurogenesis in vitro. MYT1L deficiency also causes upregulation of the main cardiac sodium channel, SCN5A, and neuronal hyperactivity, which could be restored by shRNA-mediated knockdown of SCN5A or MYT1L overexpression in postmitotic neurons. Acute application of the sodium channel blocker, lamotrigine, also rescued electrophysiological defects in vitro and behaviour phenotypes in vivo. Hence, MYT1L mutation causes both developmental and postmitotic neurological defects. However, acute intervention can normalise resulting electrophysiological and behavioural phenotypes in adulthood.

In the study, the preparation of metabolites by fermentation of Lactobacillus sp. A-2 in the desalted whey protein powder medium, separation of Lactobacillus sp. A-2 metabolites using a Diethylaminoethyl-Sephacel column (2.6 × 50 cm) and a dextran gel (Sephadex-G15) column (1.6 × 100 cm). The antioxidant activity of fractions was evaluated by the 2,2-biazo-bis(3-ethyl-benzothiazole-6-sulphonic acid) diammonium salt (ABTS) method and the oxygen radical absorbance capacity (ORAC) method. Lactobacillus sp. A-2 metabolites were isolated and purified to obtain two antioxidant active fractions DF1-1 and DEF1-1, with IC50 values of 1.21 mg/mL and 1.98 mg/mL for ABTS cation free radical scavenging activity and relative ORAC values of 257.8 µmol Trolox/g and 267.3 µmol Trolox/g, respectively. Meanwhile, the SDS-PAGE gel electrophoresis was used to analyze the molecular mass distribution of peptides in the components of DF1, DF1-1, DEF1 and DEF1-1, as a result, the components DEF1-1 contained more peptides.

Extensive interhemispheric projections connect many homotopic brain regions, including the hippocampal formation, but little is known as to how information transfer affects the functions supported by the target area. Here, we studied whether the commissural projections connecting the medial entorhinal cortices contribute to spatial coding, object coding, and memory. We demonstrate that input from the contralateral medial entorhinal cortex targets all major cell types in the superficial medial entorhinal cortex, modulating their firing rate. Notably, a fraction of responsive cells displayed object tuning and exhibited a reduction in their firing rate upon the inhibition of commissural input. In line with this finding are behavioral results that revealed the contribution of commissural input to episodic-like memory retrieval.