Vitamin D3 improves iminodipropionitrile-induced tic-like behavior in rats through regulation of GDNF/c-Ret signaling activity.

Children with chronic tic disorders (CTD), including Tourette syndrome (TS), have significantly reduced serum 25-hydroxyvitamin D [25(OH)D]. While vitamin D3 supplementation (VDS) may reduce tic symptoms in these children, its mechanism is unclear. The study aim was to investigate the effects and mechanisms of vitamin D deficiency (VDD) and VDS on TS model behavior. Forty 5-week-old male Sprague-Dawley rats were randomly divided into (n = 10 each): control, TS model, TS model with VDD (TS + VDD), or TS model with VDS (TS + VDS; two intramuscular injections of 20,000 IU/200 g) groups. The VDD model was diet-induced (0 IU vitamin D/kg); the TS model was iminodipropionitrile (IDPN)-induced. All groups were tested for behavior, serum and striatal 25(OH)D and dopamine (DA), mRNA expressions of vitamin D receptor (VDR), glial cell line-derived neurotrophic factor (GDNF), protooncogene tyrosine-protein kinase receptor Ret (c-Ret), and DA D1 (DRD1) and D2 (DRD2) receptor genes in the striatum. TS + VDD had higher behavior activity scores throughout, and higher total behavior score at day 21 compared with TS model. In contrast, day 21 TS + VDS stereotyped behavior scores and total scores were lower than TS model. The serum 25(OH)D in TS + VDD was < 20 ng/mL, and lower than control. Striatal DA of TS was lower than control. Compared with TS model, striatal DA of TS + VDD was lower, while in TS + VDS it was higher than TS model. Furthermore, mRNA expression of VDR, GDNF, and c-Ret genes decreased in TS model, and GDNF expression decreased more in TS + VDD, while TS + VDS had higher GDNF and c-Ret expressions. VDD aggravates, and VDS ameliorates tic-like behavior in an IDPN-induced model. VDS may upregulate GDNF/c-Ret signaling activity through VDR, reversing the striatal DA decrease and alleviating tic-like behavior.

[Effect of Jingfang Granules on carrageenan-induced tail thrombosis in mice based on ERK/p38 MAPK signaling pathway].

The present study explored the anti-inflammatory and anti-thrombotic mechanism of Jingfang Granules on tail thrombosis induced by carrageenan in mice. Thirty-two male ICR mice were randomly divided into a control group, a model group, a Jingfang Granules group, and a positive drug(aspirin) group, with eight mice in each group. The thrombosis model was induced by intraperitoneal injection of carrageenan(45 mg·kg~(-1)) combined with low-temperature stimulation, and the mice were treated with drugs for 7 days before modeling. Twenty-four hours after modeling, blood was detected for four blood coagulation indices in each group. The enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of plasma interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and other inflammatory factors. The tails of mice in each group were cut off to observe tail lesions and measure the length of the thrombus. The protein expression and phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase(p38 MAPK) in spleen tissues were detected by Western blot. The results showed that dark red thrombus appeared in the tails of mice in each group. The length of the black part accounted for about 40% of the total tail in the model group. Additionally, the model group showed prolonged prothrombin time(PT), increased fibrinogen(FIB) content, and shortened activated partial thromboplastin time(APTT). Compared with the model group, the groups with drug intervention displayed shortened black parts in the tail and improved four blood coagulation indices(P<0.05). As revealed by ELISA, the expression levels of TNF-α, IL-1ß, and IL-6 in the mouse plasma were significantly up-regulated in the model group, and those in the groups with drug intervention were reduced as compared with the model group(P<0.05). As demonstrated by Western blot, the protein expression and phosphorylation levels of ERK1/2 and p38 MAPK in the spleen tissues were significantly elevated in the model group, while those in the Jingfang Granules group were down-regulated as compared with the model group with a significant difference. Jingfang Granules can inhibit tail thrombosis of mice caused by carrageenan presumedly by inhibiting the activation of ERK1/2 and p38 MAPK signaling pathways.

Serum Levels of Vitamin A and Vitamin D and Their Association With Symptoms in Children With Attention Deficit Hyperactivity Disorder.

Objective: To measure levels of vitamin A (VA) and vitamin D (VD) and the symptomatic association of their co-deficiencies on attention deficit hyperactivity disorder (ADHD) in Chinese children (6-9 years). Methods: Eighty-two children (69 boys and 13 girls; mean age = 7.1 ± 0.9 years at the time of the diagnosis) with ADHD were recruited as ADHD group. A total of 106 healthy children were recruited as the healthy control (HC) group. Serum levels of retinol and 25-hydroxyvitamin D (25(OH)D) of all children were evaluated using high-performance liquid chromatography (HPLC) and HPLC-tandem mass spectrometry. The Swanson, Nolan, and Pelham IV Rating Scale (SNAP-IV) was employed to assess the clinical symptoms of ADHD. Results: Children suffering from ADHD had significantly reduced serum levels of retinol and 25(OH)D compared with those of HCs, and the prevalence of VA deficiency and VD deficiency were higher in children suffering from ADHD. Serum concentrations of 25(OH)D and retinol were linked closely with the presence or absence of ADHD after adjustment for age, body mass index, season of blood sampling, and sun exposure. Serum concentrations of 25(OH)D and retinol showed a negative correlation with the total scores of SNAP-IV. Children with ADHD as well as VA and VD co-deficiency had increased SNAP-IV total scores and ADHD inattention subscale scores. Conclusion: VA deficiency and VD deficiency in children with ADHD were increased in comparison with that in HCs. VA and VD co-deficiency associated with ADHD symptom severity. Attention should be paid to regular testing of VA levels and VD levels. However, the mechanism of VA and VD in ADHD needs to be further studied. Interventional studies on VA and VD supplementation are recommended to further verify the relationship between VA and VD co-deficiency and ADHD.

Successive clinical application of vitamin D and bumetanide in children with autism spectrum disorder: A case report.

RATIONALE: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complex interactions between genetic and environmental factors. Recent studies suggest that Vitamin D3 or bumetanide therapy may improve the core symptoms of ASD in some individuals. However, there are no guidelines that provide clinicians with evidence-based treatment regimens for the use of these therapies in ASD. PATIENT CONCERNS: A 30-month-old female was referred to our department because she did not respond when her name was called. DIAGNOSIS: The patient was diagnosed with ASD by a team of autism experts according to American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. INTERVENTIONS: The patient was administered Vitamin D3 150,000 IU intramuscularly once a month and Vitamin D3 800 IU orally each day. After 6 months, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Subsequently, oral bumetanide 0.5 mg twice daily was initiated. OUTCOMES: The patient's symptoms remained unchanged after 6 months of Vitamin D3 supplementation, and her serum 25 (OH) D levels had reached 52.4 ng/mL. At the parent's request, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Thereafter, bumetanide was initiated. After 1 month of bumetanide, the patient's Childhood Autism Rating Scale score was 26, which is below the cutoff score for ASD. This case report suggests that Vitamin D3 and bumetanide target different mechanisms in the pathogenesis of ASD. LESSONS: Based on these observations, we discuss three possible scenarios for Vitamin D3 supplementation and propose that bumetanide should be initiated if Vitamin D3 supplementation is ineffective (identifier ChiCTR-CCC-13004498).

Clinical improvement following vitamin D3 supplementation in children with chronic tic disorders.

PURPOSE: Vitamin D deficiency has been found in children with chronic tic disorders (CTDs). Our previous data showed that serum 25-hydroxyvitamin D [25(OH)D] level in children with CTDs was lower than that of the healthy controls and lower serum 25(OH)D level was associated with increased severity of the tic disorder. Thus, we intend to further verify this phenomenon and examine the effect of vitamin D3 on CTDs. PATIENTS AND METHODS: In total, 120 children with CTDs and 140 normal controls were enrolled in this study, with 36/120 of those in the CTD group receiving vitamin D3 treatment for 3 months. The Yale Global Tic Severity Scale (YGTSS) and Clinical Global Impression of Severity of Illness (CGI-SI) were, respectively, used to evaluate the tic severity. High-performance liquid chromatography and tandem mass spectrometry were used to measure serum 25(OH)D level. RESULTS: Those children with CTDs exhibited significantly lower 25(OH)D levels than did healthy controls, and these reduced 25(OH)D levels were linked to increasing severity of tic symptoms. After treatment with supplemental vitamin D3, serum 25(OH)D level and scores of YGTSS total, motor tics, phonic tics, total tic, impairment, and CGI-SI improved significantly in children with CTDs without any adverse reactions. CONCLUSION: Supplementation vitamin D3, given its low cost and excellent safety, may be an effective means of improving symptoms in certain children with CTDs.

[Research advances in the management of autism spectrum disorders in children].

Autism spectrum disorders (ASD) are a group of developmental dysfuntion of nervous system characterized by social interaction and communication disorders, restricted interests and repetitive stereotyped behaviors. The incidence of ASD has been increasing through the world. Some studies have shown that early reasonable individualized comprehensive intervention can obviously improve the prognosis of children with ASD. The etiology of ASD is unclear now, and behavioral and developmental intervention is the main therapy for ASD. The reasonable application of some drugs can improve the efficacy of the behavioral intervention for concomitant symptoms in ASD. With the in-depth study of the pathogenesis of ASD, bumetanide, oxytocin, vitamin D and hyperbaric oxygen therapy have been found to be promising for the improvement of core symptoms of ASD. This article reviews the research advances in the behavioral and developmental intervention and drug therapy for ASD.

Neonatal maternal deprivation response and developmental changes in gene expression revealed by hypothalamic gene expression profiling in mice.

Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.