Saito Kuniaki

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, social deficits, and cognitive impairments. Maternal use of valproic acid (VPA) during pregnancy is associated with an increased risk of ASD in offspring. The prevailing pathophysiological hypothesis for ASD involves excitation/inhibition (E/I) imbalances and serotonergic dysfunction. Here, we investigated the association between glutamatergic-serotonergic neuronal interactions and ASD-like behaviors in mice exposed to prenatal VPA. Prenatal VPA exposure induced excessive repetitive self-grooming behavior and impaired social behavior and object recognition memory in young adult period. Prenatal VPA mice showed hyper-glutamatergic function (increase in basal extracellular glutamate levels and CaMKII phosphorylation) and hypo-serotonergic function (decrease in 5-hydroxyindoleacetic acid and stimulation-induced serotonin [5-HT] release, but an increase in 5-HT transporter expression) in the prefrontal cortex. Treatment with a low-affinity NMDA receptor antagonist (memantine), a selective 5-HT reuptake inhibitor (fluoxetine), and a 5-HT_1A receptor agonist (tandospirone) attenuated both the increase in CaMKII phosphorylation and ASD-like behavior of prenatal VPA mice. Opto-genetic activation of the serotonergic neuronal system attenuated impairments in social behavior and object recognition memory in prenatal VPA mice. WAY-100635—a 5-HT_1A receptor antagonist—antagonized the effect of fluoxetine on impaired social behavior and object recognition memory. These results suggest that E/I imbalance and ASD-like behavior are associated with hypo-serotonergic receptor signaling through 5-HT_1A receptors in prenatal VPA mice.

High salt (HS) intake induces hypertension and cognitive impairment. Preventive strategies include against dietary supplements. Soybean lecithin is a widely used phospholipid supplement. Lysolecithin is important in cell signaling, digestion, and absorption. This study aimed to investigate the effects of lysophosphatidylcholine containing >70% of the total phospholipids (LPC70), on hypertension and cognitive impairment induced in mice by HS intake. Mice were provided with HS solution (2% NaCl in drinking water) with or without LPC70 for 12 weeks. Blood pressure, cognitive function, and inflammatory response of intestine were determined. Hypertension and impaired object recognition memory induced by HS intake were implicated with increased inducible nitric oxide synthase in the small intestine and tau hyperphosphorylation in the prefrontal cortex. LPC70 treatment prevented cognitive impairment by suppressing inducible nitric oxide synthase and tau hyperphosphorylation. LPC70 may be valuable as a functional food component in preventing HS-induced cognitive impairment.

BACKGROUND: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes. METHOD: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC). RESULTS: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21-35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8-14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214-0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217-0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170-40.833, p = 0.032). CONCLUSIONS: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.