Galacto-N-biose is neuroprotective against glutamate-induced excitotoxicity in vitro.

Galacto-N-biose (GNB: Galß1-3GalNAc) is an O-glycan disaccharide core moiety that is a core component of mucin in the gastrointestinal tract; however, the physiological properties of GNB are not well understood. Glutamate excitotoxicity causes neuronal death in acute neurological disorders including stroke, trauma, and neurodegenerative disease. Therefore the discovery of drugs to treat glutamate excitotoxicity is an important goal. Here, we report that GNB is neuroprotective against glutamate-induced excitotoxicity. We treated 14-15 days in vitro cultured rat cortical neurons with 0.1-1000nM GNB together with 30µm glutamate for various durations. Short-term (3h) GNB treatments showed a modest neuroprotective effect against glutamate neurotoxicity, however, long-term (24h) GNB treatment conferred significant neuroprotective effects, as shown by both MTT and immunocytochemical assays. Prolonged GNB treatment did not alter glutamate-induced calcium influx, but did induce antioxidant-related gene expression. Furthermore, GNB treatment did not induce cell death or alter synaptic connections. These data suggest that GNB is a potential candidate drug that protects against glutamate excitotoxicity without affecting cell viability and synaptic connections.

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity.

Citrinin, a natural mycotoxin that is found in fermented foods, is known as a cytotoxin and nephrotoxin. Exposure to high doses of citrinin result in apoptosis; however, the effects of low doses are not fully understood. Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and other neurodegenerative diseases. Here, we show the neuroprotective effect of low doses of citrinin against glutamate-induced excitotoxicity. We examined the effect of citrinin exposure on glutamate-induced cell death in cultured rat cortical neurons under two conditions: simultaneous treatment with citrinin 0.1 to 1,000 nM and glutamate (30 µM) for 1, 3 hr; the same simultaneous treatment for 3 hr after pretreatment with citrinin for 21 hr. Both the MTT and immunocytochemical assay showed significant neuroprotective effects at several doses and exposure times tested. All concentrations of citrinin tested showed no remarkable cell death following 14-day exposure, and no marked alterations to synapses. These data suggest that low doses of citrinin can be used as a neuroprotective agent against glutamate-induced excitotoxicity without additional harmful cellular alterations.

Mouse models of mutations and variations in autism spectrum disorder-associated genes: mice expressing Caps2/Cadps2 copy number and alternative splicing variants.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disturbances in interpersonal relationships and behavior. Although the prevalence of autism is high, effective treatments have not yet been identified. Recently, genome-wide association studies have identified many mutations or variations associated with ASD risk on many chromosome loci and genes. Identification of the biological roles of these mutations or variations is necessary to identify the mechanisms underlying ASD pathogenesis and to develop clinical treatments. At present, mice harboring genetic modifications of ASD-associated gene candidates are the best animal models to analyze hereditary factors involved in autism. In this report, the biological significance of ASD-associated genes is discussed by examining the phenotypes of mouse models with ASD-associated mutations or variations in mouse homologs, with a focus on mice harboring genetic modifications of the Caps2/Cadps2 (Ca2+-dependent activator protein for secretion 2) gene.