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Prenatal Methamphetamine Exposure Impairs Helping Behaviour in Male Offspring: The Possible Role of miR-223 and NLRP3 Inflammasomes in the Amygdala 产前甲基苯丙胺暴露会损害雄性后代的帮助行为:杏仁核中miR-223和NLRP3炎症小体的可能作用
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-26 DOI: 10.1002/jdn.10410
Fariba Khodagholi, Mitra Ansari Dezfouli, Neda Yazdanfar, Seyed Khalil Rashidi, Arman Zeinaddin Meymand, Pegah Javadpour, Seyed Hamidreza Mirbehbahani, Nayereh Zare

The increasing prevalence of methamphetamine abuse among women, particularly pregnant females, is a global concern. Methamphetamine can readily cross anatomical barriers like the blood-placenta barrier and cause detrimental impacts on the growing fetus. The current research evaluated the effects of prenatal methamphetamine exposure on helping behaviour and neuroinflammatory cascade in the amygdala of male offspring. On the tenth day of pregnancy, female rats received either saline or methamphetamine (5 mg/kg) until delivery. Once the offspring reached 21 days of age, the male ones were sep arated from their mothers and housed with normal male rats. An empathy-like behaviour test, which measured helping behaviour towards the cage mate, was conducted. The expression levels of miR-223-3p, NLRP3, Caspase 1, and gasdermin D (GSDMD) were evaluated in the amygdala of male offspring. Moreover, interleukin-1β (IL-1β) protein level was measured. Findings of this study revealed that male offspring exposed to methamphetamine during pregnancy had impaired helping behaviour. At the molecular level, prenatal methamphetamine exposure decreased miR-223-3p and increased inflammasome signaling by raising the levels of NLRP3, caspase-1, and GSDMD along with IL-1β levels. These findings indicate that prenatal methamphetamine exposure impairs emotional behaviour and activates inflammasome pathway in the amygdala.

妇女、特别是孕妇滥用甲基苯丙胺的现象日益普遍,这是一个全球关切的问题。甲基苯丙胺很容易穿过血胎盘屏障等解剖屏障,对正在发育的胎儿造成有害影响。目前的研究评估了产前甲基苯丙胺暴露对雄性后代杏仁核的帮助行为和神经炎症级联的影响。妊娠第10天,雌性大鼠分别给予生理盐水或甲基苯丙胺(5 mg/kg),直至分娩。一旦后代长到21天龄,雄性老鼠就会与它们的母亲分开,与正常的雄性老鼠住在一起。研究人员进行了一项类似移情的行为测试,测量了它们对笼子同伴的帮助行为。检测雄性后代杏仁核中miR-223-3p、NLRP3、Caspase 1和gasdermin D (GSDMD)的表达水平。同时测定白细胞介素-1β (IL-1β)蛋白水平。这项研究的结果表明,在怀孕期间接触甲基苯丙胺的雄性后代会损害帮助行为。在分子水平上,产前甲基苯丙胺暴露通过提高NLRP3、caspase-1和GSDMD的水平以及IL-1β水平,降低了miR-223-3p并增加了炎性体信号传导。这些发现表明,产前暴露于甲基苯丙胺会损害情绪行为,并激活杏仁核中的炎性体途径。
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引用次数: 0
Prenatal Exposure to Quercetin Protects Against Methimazole-Induced Reflexive Motor Behavior and Oxidative Stress Markers in Mouse Offspring 产前暴露于槲皮素对小鼠后代甲巯咪唑诱导的反射性运动行为和氧化应激标志物有保护作用。
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-26 DOI: 10.1002/jdn.10409
Sara Zahedi, Shahin Hassanpour, Seeyamak Mashhadyrafie

Quercetin is a natural flavonoid and one of the most powerful antioxidants. Due to its wide range of biological properties, it may improve cognitive and physical performance by affecting nervous tissue. The current study is aimed at determining the effect of prenatal exposure to quercetin against methimazole (MMI)-induced hypothyroidism on reflexive motor behavior in mouse offspring. In this study, 40 female mice were mated with 12 fertile male NMRI mice, and the pregnant mice were divided into four groups. Group 1 served as the control, Group 2 received 0.2% MMI in drinking water, Group 3 received 150 mg/kg quercetin via gavage, and Group 4 received both 0.2% MMI in drinking water and 150 mg/kg quercetin via gavage from Days 1 to 9 of gestation. The offspring were assessed for reflexive motor behaviors and conditioned fear. Catalase (CAT), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels in the neonates were also examined. The findings indicated that exposure to quercetin led to improved ambulation, hindlimb suspension, grip strength, front-limb suspension, hindlimb foot angle, negative geotaxis, surface righting, and conditioned fear behaviors in the offspring (p < 0.05). Additionally, quercetin reduced levels of MDA and increased levels of SOD, GPx, and CAT in the brain tissue (p < 0.05). These results suggested that quercetin exposure during pregnancy has positive effect on reflexive motor behaviors and antioxidant levels in mouse offspring.

槲皮素是一种天然的类黄酮,也是最强大的抗氧化剂之一。由于其广泛的生物学特性,它可以通过影响神经组织来改善认知和身体表现。本研究旨在确定产前暴露槲皮素对抗甲巯咪唑(MMI)诱导的甲状腺功能减退症对小鼠后代反射性运动行为的影响。在这项研究中,40只雌性小鼠与12只可生育的雄性NMRI小鼠交配,将怀孕的小鼠分为四组。第1组为对照组,第2组为0.2% MMI饮用水,第3组为150 mg/kg槲皮素灌胃,第4组为0.2% MMI饮用水和150 mg/kg槲皮素灌胃。评估后代的反射性运动行为和条件性恐惧。同时检测新生儿过氧化氢酶(CAT)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)水平。结果表明,暴露于槲皮素可改善后代的行走、后肢悬吊、握力、前肢悬吊、后肢足角、负地向性、表面扶正和条件性恐惧行为
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引用次数: 0
Lutein Exerts Antioxidant and Neuroprotective Role on Schizophrenia-Like Behaviours in Mice 叶黄素对小鼠精神分裂症样行为的抗氧化和神经保护作用
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-26 DOI: 10.1002/jdn.10407
Helia Aziziha, Shahin Hassanpour, Morteza Zendehdel

Schizophrenia is an esteemed neuropsychiatric condition delineated by the manifestation which role of the N-methyl-D-aspartate receptor (NMDAR) is important. Lutein administration exhibits protective effects via NMDA receptors. Thus, the main goal of this research was to investigate how lutein can possibly act as an antioxidant and provide protection for the brain against schizophrenia-like behaviours in mice. In total, 24 male mice were divided into four experimental groups: control, ketamine (20 mg/kg, i.p), lutein (10 mg/kg, i.p) and a mix of ketamine (20 mg/kg, i.p) and lutein (10 mg/kg, i.p). Lutein was given to the mice for 30 days, while ketamine was given from Days 16 to 30 to create a model of schizophrenia in the animals. After giving drugs, schizophrenia-like behaviours were evaluated with novel object recognition test (NORT), tail suspension test (TST), forced swimming test (FST) and open field tests. Furthermore, the amounts of brain malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were assessed. The findings showed a noteworthy decrease in the crossings during the open field test and increase in immobility duration in the TST and FST as a result of ketamine administration (p < 0.05). Prior administration of lutein showed a decrease in the detrimental effects of ketamine on the open field assay, along with a reduction in immobility duration in the TST and FST experiments (p < 0.05). Administration of ketamine caused a notable reduction in the discrimination index, while pretreatment with lutein was associated with a rise in the discrimination index (p < 0.05). Furthermore, the administration of ketamine significantly increased the levels of MDA in both cortical and subcortical regions, which were then reduced by lutein pretreatment (p < 0.05). Moreover, ketamine use led to a significant decrease in tissue SOD, GPx and CAT levels in both cortical and subcortical brain regions in mice (p < 0.05). Nonetheless, lutein pretreatment significantly enhanced SOD, GPx and CAT levels in cortical and subcortical regions (p < 0.05). These results indicate that lutein may have protective effects on the brain to improve behavioural problems.

精神分裂症是一种受人尊敬的神经精神疾病,其表现形式是n -甲基- d -天冬氨酸受体(NMDAR)的重要作用。叶黄素通过NMDA受体发挥保护作用。因此,这项研究的主要目标是研究叶黄素如何可能作为抗氧化剂,并为小鼠的大脑提供保护,防止精神分裂症样行为。将24只雄性小鼠分为4个实验组:对照组、氯胺酮(20 mg/kg,灌胃)、叶黄素(10 mg/kg,灌胃)和氯胺酮(20 mg/kg,灌胃)和叶黄素(10 mg/kg,灌胃)混合组。叶黄素被给予小鼠30天,而氯胺酮从第16天到第30天被给予,以在动物身上建立精神分裂症模型。给予药物后,采用新目标识别测试(NORT)、悬尾测试(TST)、强迫游泳测试(FST)和野外测试评估精神分裂症样行为。测定大鼠脑组织丙二醛(MDA)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的含量。结果显示,由于氯胺酮的施用,在野外试验期间,交叉次数显著减少,在TST和FST中不活动的持续时间增加(p
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引用次数: 0
Folinic acid as a treatment for autism in children: A within-subjects open-label study on safety and efficacy 亚叶酸治疗儿童自闭症:一项关于安全性和有效性的受试者内开放标签研究
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-19 DOI: 10.1002/jdn.10402
Chui Mae Wong, Charmain Samantha Tan, Hwan Cui Koh, Xinyi Gan, Szu Liang Hie, Seyed Ehsan Saffari, Joo Guan Yeo, Joyce Ching Mei Lam

The folate cycle has been implicated in the pathophysiology of autism due to its role in the glutathione oxidative stress pathway, amino acid and DNA methylation reactions, and neurotransmitter synthesis pathway. Previous research on folinic acid supplementation in autistic children has suggested potential benefits. The primary aim of this pilot study was to determine the safety, feasibility and efficacy of oral folinic acid in improving communication and behaviour in autistic children. Ten autistic children were recruited into an open-label pre-post treatment within-subjects design study. At T = 0, 12 and 24 weeks, participants underwent safety evaluations, standardized assessments of language, autism symptoms, adaptive skills and global illness severity, and eye-gaze tracking. During the control period (0–12 weeks), participants continued with standard care. In the treatment period (12–24 weeks), participants took oral folinic acid at 2 mg/kg/day. All 10 children (nine boys, one girl; aged 4–8 years), successfully consumed oral folinic acid supplements with no adverse events. There was a reduction in Pervasive Developmental Disorder Behavior Inventory (PDDBI) Autism Composite T-score with treatment (mean [SD] T-score 49.2 [8.89] pre-treatment, 44.6 [6.19] post-treatment, p = 0.103). Although this difference was not statistically significant due to the small sample size, the effect size was medium-large, indicating that, as a group, there were clinically meaningful changes in PDDBI T-scores. There were also trends towards gains in communication scores and overall Clinical Global Impression scores. Folinic acid is a safe and feasible potential treatment for autism, and results from this pilot justify the need for a larger placebo-controlled trial.

叶酸循环由于其在谷胱甘肽氧化应激途径、氨基酸和DNA甲基化反应以及神经递质合成途径中的作用而与自闭症的病理生理有关。先前对自闭症儿童补充叶酸的研究表明了潜在的益处。本初步研究的主要目的是确定口服亚叶酸在改善自闭症儿童沟通和行为方面的安全性、可行性和有效性。10名自闭症儿童被招募到一项开放标签的治疗前后受试者设计研究中。在T = 0、12和24周时,参与者接受了安全性评估、语言、自闭症症状、适应技能和整体疾病严重程度的标准化评估,以及眼球追踪。在对照期(0-12周),参与者继续接受标准治疗。在治疗期间(12-24周),参与者以2 mg/kg/天的剂量口服亚叶酸。所有10个孩子(9个男孩,1个女孩;年龄4-8岁),成功服用口服叶酸补充剂,无不良事件。治疗后广泛性发育障碍行为量表(PDDBI)自闭症综合t评分降低(治疗前平均t评分为49.2[8.89],治疗后平均t评分为44.6 [6.19],p = 0.103)。虽然由于样本量小,这一差异没有统计学意义,但效应量为中大型,表明作为一个组,PDDBI t评分有临床意义的变化。沟通得分和临床总体印象得分也有上升的趋势。亚叶酸是一种安全可行的治疗自闭症的潜在方法,该试验的结果证明需要进行更大规模的安慰剂对照试验。
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引用次数: 0
The effect of tactile stimulation on spatial memory and hippocampal neuronal density in male rats with sensory deprivation during a critical period 触觉刺激对感觉剥夺期雄性大鼠空间记忆和海马神经元密度的影响。
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-12 DOI: 10.1002/jdn.10404
Suheda Ozkan, Pınar Oz, Yaren Erdogan, Melisa Akpinar, Aya Sahsahi, Zehra Gecen

It is well known that sensory information driven from whiskers serves as an example of tactile perception in rodents, and plays an important role in social behavior, environmental exploration, and decision-making processes, the influence of manipulations performed during the development of whiskers, on learning has been received little attention in the literature. This study aimed to evaluate the effect of tactile stimulation (TS) on spatial memory performance and neuronal density in the hippocampus during adulthood in early sensory-deprived rats. Wistar albino male rats were divided into four groups: control (CTL), bilateral whisker trimming (BWT), tactile stimulation (TS), and bilateral whisker trimming+tactile stimulation (BWT + TS). All whiskers were trimmed between P0–10, a critical period for whisker development. TS was applied from P3 to P21 using a soft brush. In this study, the 8-arm radial maze test was conducted from postnatal days 77 to 81 to assess spatial memory Animals sacrificed by intracardial perfusion and neuronal density in CA1, CA3, vDG, and dDG regions of the hippocampus were evaluated by Nissl staining. TS exposure negatively affected spatial memory performance and hippocampal neuronal density compared to BWT. We conclude that TS in healthy offspring can cause stress by interrupting maternal care, given the vulnerability of early development. On the contrary, the sensory deprivation protocol in this study was terminated at a time of high homeostatic plasticity and did not produce complete whisker deprivation, have triggered learning by inducing moderate stress early in development.

众所周知,由须驱动的感觉信息是啮齿动物触觉感知的一个例子,在社会行为、环境探索和决策过程中起着重要作用,但在须发育过程中进行的操作对学习的影响在文献中很少受到关注。本研究旨在探讨触觉刺激对早期感觉剥夺大鼠成年期空间记忆表现和海马神经元密度的影响。将Wistar白化雄性大鼠分为对照组(CTL)、双侧须修剪组(BWT)、触觉刺激组(TS)和双侧须修剪+触觉刺激组(BWT + TS)。所有的胡须都是在P0-10之间修剪的,这是胡须发育的关键时期。使用软刷将TS从P3涂抹到P21。本研究在出生后第77 ~ 81天进行8臂径向迷宫实验,评估空间记忆。采用心内灌注处死动物,采用尼氏染色法评估海马CA1、CA3、vDG、dDG区神经元密度。与BWT相比,TS暴露对空间记忆表现和海马神经元密度有负面影响。我们的结论是,考虑到早期发育的脆弱性,健康后代的TS可以通过中断母体护理而引起压力。相反,本研究中的感觉剥夺方案终止于高稳态可塑性的时期,并没有产生完全的晶须剥夺,通过在发育早期诱导适度的压力来触发学习。
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引用次数: 0
Breaking boundaries: A systematic review of the application of non-invasive brain stimulation symptoms and sleep parameters in people with ADHD 突破界限:对非侵入性脑刺激症状和睡眠参数在ADHD患者中的应用的系统回顾。
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-10 DOI: 10.1002/jdn.10401
Renato Mendes dos Santos, Victor Marinho, Sabrina Nayara de Araújo Val, Ariel Soares Teles, Daniel Lima Sousa, Victor Hugo do Vale Bastos, Leonardo Peres de Souza, Angelina Ketllen Cachoeira de Sousa, Gabryella Stefane Firmino de Moraes, Silmar Teixeira

Background

Studies of non-invasive treatments such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) can contribute in an alternative way to the symptoms treatment and changes in sleep patterns in attention deficit hyperactivity disorder (ADHD), due to some scientific evidence of action on cognition and clinical characteristics.

Aim

The aim of this systematic review was to evaluate studies of non-invasive brain stimulation using rTMS and tDCS on symptoms and sleep parameters in people with ADHD, in order to synthesize the main findings on intervention effects.

Methodology

A systematic review was carried out using the PRISMA protocol in the PubMed/Medline, Embase, PsycInfo, CINAHL, PEDro and Central—Cochrane library databases were initially carried out on 14 March 2024 and repeated until September 2024. Randomized clinical trials evaluating the effect of rTMS and tDCS on symptoms and changes in sleep pattern in people with ADHD were included. Primary outcomes were total severity of ADHD symptoms and sleep quality assessed by questionnaires and instrument measures.

Results

The review evidenced only positive findings in five studies for tDCS in some cognitive functions, ADHD symptoms and improvement in sleep parameters, being results with reduced efficacy due to the high heterogeneity in the experimental protocols.

Conclusion

The findings show limited evidence; however, it is suggested that the combined use of non-invasive stimulation with other approaches, such as cognitive training, may improve the intervention effect. It is also important to consider limitations such as heterogeneity in clinical protocols, selection of participants with ADHD, including dosage and frequency. These factors should be explored in future research to optimize the application of these therapies.

背景:重复性经颅磁刺激(rTMS)和经颅直流电刺激(tDCS)等非侵入性治疗方法的研究可以为注意缺陷多动障碍(ADHD)的症状治疗和睡眠模式的改变做出贡献,因为一些科学证据表明它们对认知和临床特征有作用。目的:本系统综述的目的是评价采用rTMS和tDCS的无创脑刺激对ADHD患者症状和睡眠参数的影响,以综合干预效果的主要研究结果。方法:采用PRISMA协议对PubMed/Medline、Embase、PsycInfo、CINAHL、PEDro和Central-Cochrane图书馆数据库进行系统评价,最初于2024年3月14日进行,并重复至2024年9月。包括评估rTMS和tDCS对ADHD患者症状和睡眠模式改变影响的随机临床试验。主要结果是ADHD症状的总严重程度和通过问卷调查和仪器测量评估的睡眠质量。结果:本综述仅证实了5项tDCS在某些认知功能、ADHD症状和睡眠参数改善方面的阳性结果,由于实验方案的高度异质性,这些结果的有效性降低。结论:研究结果证据有限;然而,建议将非侵入性刺激与其他方法(如认知训练)联合使用,可能会提高干预效果。同样重要的是要考虑局限性,如临床方案的异质性,ADHD患者的选择,包括剂量和频率。这些因素应在未来的研究中加以探讨,以优化这些疗法的应用。
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引用次数: 0
Brain-derived neurotrophic factor as a promising neuromarker which could predict psychomotor developmental impairment in children with unrepaired congenital heart defects 脑源性神经营养因子作为预测未修复先天性心脏病患儿精神运动发育障碍的一种有前景的神经标志物。
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-10 DOI: 10.1002/jdn.10400
Lacramioara Eliza Chiperi, Asmaa Carla Hagau, Cristina Tecar, Adina Hutanu, Iolanda Muntean

Introduction

The aim of the study was to assess the predicting value of neuromarkers for psychomotor performances of congenital heart defect (CHD) patients before surgery, as until now the researchers only evaluated neuromarkers after the surgical treatment of the CHD.

Methods

This cross-sectional study included children with CHD who did not receive treatment (interventional or cardiac surgery). Psychomotor development was evaluated using the Denver II Screening Test. Blood samples were collected for neuromarkers analysis: neuron-specific enolase (NSE), protein S100 (pS100), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP).

Results

We enrolled 77 children. Patients with CHD experienced more frequent developmental delays compared to healthy children (12–34% in the non-cyanotic group and 26–74% in the cyanotic group). The association between type of CHD and psychomotor impairment was statistically significant (p < 0.0001, RR = 2.604, CI = 2.07–3.26). Neuromarkers value was compared between cyanotic and non-cyanotic groups: NSE and BDNF values were higher in the cyanotic group, respectively, pS100 and GFAP had slightly higher values in the non-cyanotic group. A correlation coefficient of 0.35 (p = 0.023) was obtained between psychomotor development and BDNF level. An AUC of 0.72 was obtained for psychomotor development and BDNF in ROC analysis with the cut-off value of 5895 pg/ml.

Conclusion

BDNF is showing moderate discriminative ability in predicting psychomotor development outcomes in pediatric patients with CHD.

导论:本研究的目的是评估神经标志物对先天性心脏缺陷(CHD)患者术前精神运动表现的预测价值,因为到目前为止,研究人员只评估了CHD手术治疗后的神经标志物。方法:本横断面研究纳入未接受治疗(介入性或心脏手术)的冠心病患儿。使用丹佛II筛选测试评估精神运动发展。采集血样进行神经标志物分析:神经元特异性烯醇化酶(NSE)、蛋白S100 (pS100)、脑源性神经营养因子(BDNF)、胶质原纤维酸性蛋白(GFAP)。结果:我们招募了77名儿童。与健康儿童相比,冠心病患者经历更频繁的发育迟缓(非紫绀组为12-34%,紫绀组为26-74%)。结论:BDNF在预测小儿冠心病患者精神运动发育结局方面具有中等判别能力。
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引用次数: 0
A patient with a PTPN11 gene variant complicated with Chiari I malformation and syringomyelia and a review of literatures PTPN11基因变异合并Chiari I型畸形和脊髓空洞1例并文献复习。
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-09 DOI: 10.1002/jdn.10396
Zhi Yi, Jiao Xue, Zhenfeng Song, Fei Li, Chengqing Yang, Ying Zhang
<div> <section> <h3> Background</h3> <p>According to previous literature reports, <i>PTPN11</i> gene variants account for approximately 50% of Noonan syndrome (NS) cases and 85% of Leopard syndrome (LS) cases. Several patients who were diagnosed with NS or LS complicated with Chiari I malformation (CIM) and/or syringomyelia have been reported to have a <i>PTPN11</i> variant. However, it is not always clear whether the association between CIM and/or syringomyelia and <i>PTPN11</i> variants is real or random. We try to explain this phenomenon by reporting a clinical case and making a mini-review.</p> </section> <section> <h3> Methods</h3> <p>We retrospectively described a clinical case in detail and made a genetic test on the proband and her family members using whole-exome sequencing. And made a review of the related literatures.</p> </section> <section> <h3> Results</h3> <p>The patient was manifesting progressive abnormal gait and muscle weakness for more than 2 years before she was admitted to our hospital at the age of 5 years and 2 months. On examination, she looked frail and slender. She had short stature, mild intellectual disability, decreased muscle strength in the left limb, thinner left limb, left hollow foot and foot drop, weakened left knee and Achilles tendon reflexes and a positive left Babinski sign. She looked timid and had very little expressive language. MRI of the brain and spine revealed CIM and syringomyelia with hydrops. Cardiac ultrasonography revealed an ostium secundum defect. ECG examination showed no abnormalities. She received a spinal cavity subarachnoid shunt; the symptoms were relieved to some extent, and the cavity in the lumbar vertebrae was significantly reduced after the surgery. Genetic testing found a variant, c. 922A>G (p. Asn308Asp) in the <i>PTPN11</i> gene. Both parents were wild-type at this locus. A literature review found that 31 patients with NS or LS were complicated with CIM, syringomyelia or both. Together with our patient, a total of six patients in this group had the <i>PTPN11</i> gene variant. Among them, four were complicated with both CIM and syringomyelia, and two were complicated with CIM only.</p> </section> <section> <h3> Conclusions</h3> <p>We report another case with a <i>PTPN11</i> variant that was complicated with both CIM and syringomyelia. It suggests that CIM and syringomyelia may be clinical manifestations of <i>PTPN11</i> variation-related diseases. This phenomenon may be underrated due to limitations of genetic diagnostic methods in the past. We strongly suggest routine craniocerebral and spinal MRI scans and genetic testing for patients suspected of having NS or
背景:根据文献报道,PTPN11基因变异约占Noonan综合征(NS)病例的50%和Leopard综合征(LS)病例的85%。据报道,一些被诊断为NS或LS合并Chiari I型畸形(CIM)和/或脊髓空洞的患者携带PTPN11变异。然而,CIM和/或脊髓空洞和PTPN11变异之间的关联是真实的还是随机的,这一点并不总是清楚的。我们试图通过报告一个临床病例和做一个小回顾来解释这一现象。方法:回顾性详细描述1例临床病例,采用全外显子组测序对先证者及其家族成员进行基因检测。并对相关文献进行了综述。结果:患者于5岁零2个月入院前,表现为进行性步态异常和肌无力2年多。在检查时,她看起来虚弱而苗条。她身材矮小,轻度智力残疾,左肢体肌肉力量下降,左肢体较瘦,左足空心,足下垂,左膝和跟腱反射减弱,左巴宾斯基征阳性。她看上去胆小怕事,几乎不会表达什么语言。脑和脊柱MRI显示CIM和脊髓空洞伴积水。心脏超声检查显示第二口缺损。心电图检查未见异常。她接受了脊髓腔蛛网膜下腔分流术;术后症状有所缓解,腰椎腔明显缩小。基因检测在PTPN11基因中发现了c. 922A>G (p. Asn308Asp)的变体。双亲在这个位点都是野生型。文献回顾发现31例NS或LS患者合并CIM、脊髓空洞或两者兼有。加上本例患者,本组共有6例患者携带PTPN11基因变异。其中4例合并CIM和脊髓空洞,2例仅合并CIM。结论:我们报告了另一例PTPN11变异合并CIM和脊髓空洞的病例。提示CIM和脊髓空洞可能是PTPN11变异相关疾病的临床表现。由于过去遗传诊断方法的局限性,这种现象可能被低估了。我们强烈建议对怀疑患有NS或LS的患者进行常规颅脑和脊柱MRI扫描和基因检测。
{"title":"A patient with a PTPN11 gene variant complicated with Chiari I malformation and syringomyelia and a review of literatures","authors":"Zhi Yi,&nbsp;Jiao Xue,&nbsp;Zhenfeng Song,&nbsp;Fei Li,&nbsp;Chengqing Yang,&nbsp;Ying Zhang","doi":"10.1002/jdn.10396","DOIUrl":"10.1002/jdn.10396","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;According to previous literature reports, &lt;i&gt;PTPN11&lt;/i&gt; gene variants account for approximately 50% of Noonan syndrome (NS) cases and 85% of Leopard syndrome (LS) cases. Several patients who were diagnosed with NS or LS complicated with Chiari I malformation (CIM) and/or syringomyelia have been reported to have a &lt;i&gt;PTPN11&lt;/i&gt; variant. However, it is not always clear whether the association between CIM and/or syringomyelia and &lt;i&gt;PTPN11&lt;/i&gt; variants is real or random. We try to explain this phenomenon by reporting a clinical case and making a mini-review.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We retrospectively described a clinical case in detail and made a genetic test on the proband and her family members using whole-exome sequencing. And made a review of the related literatures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The patient was manifesting progressive abnormal gait and muscle weakness for more than 2 years before she was admitted to our hospital at the age of 5 years and 2 months. On examination, she looked frail and slender. She had short stature, mild intellectual disability, decreased muscle strength in the left limb, thinner left limb, left hollow foot and foot drop, weakened left knee and Achilles tendon reflexes and a positive left Babinski sign. She looked timid and had very little expressive language. MRI of the brain and spine revealed CIM and syringomyelia with hydrops. Cardiac ultrasonography revealed an ostium secundum defect. ECG examination showed no abnormalities. She received a spinal cavity subarachnoid shunt; the symptoms were relieved to some extent, and the cavity in the lumbar vertebrae was significantly reduced after the surgery. Genetic testing found a variant, c. 922A&gt;G (p. Asn308Asp) in the &lt;i&gt;PTPN11&lt;/i&gt; gene. Both parents were wild-type at this locus. A literature review found that 31 patients with NS or LS were complicated with CIM, syringomyelia or both. Together with our patient, a total of six patients in this group had the &lt;i&gt;PTPN11&lt;/i&gt; gene variant. Among them, four were complicated with both CIM and syringomyelia, and two were complicated with CIM only.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We report another case with a &lt;i&gt;PTPN11&lt;/i&gt; variant that was complicated with both CIM and syringomyelia. It suggests that CIM and syringomyelia may be clinical manifestations of &lt;i&gt;PTPN11&lt;/i&gt; variation-related diseases. This phenomenon may be underrated due to limitations of genetic diagnostic methods in the past. We strongly suggest routine craniocerebral and spinal MRI scans and genetic testing for patients suspected of having NS or","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"85 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxidative stress and apoptosis of the spinal cord in a rat model of retinoic acid-induced neural tube defects 维甲酸致神经管缺损大鼠脊髓氧化应激和细胞凋亡的研究。
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-05 DOI: 10.1002/jdn.10399
Peng Wu, Nan Shen, Shaoguang Feng, Weiguang Liu, Jun Wang, Chen Wang

Neural tube defects (NTDs) are severe congenital anomalies that significantly impact the central nervous system, arising from the neural tube's failure to close during early embryogenesis. In this study, we investigated NTDs and associated pathophysiological mechanisms in foetal rats following exposure to all-trans retinoic acid (atRA). Out of 168 embryos from 15 pregnant rats in the experimental group, 78% displayed NTDs with notable spinal deformities, primarily in the lumbar-sacral region, similar to human cases. Body weight and crown-rump length (CRL) measurements indicated significant growth impairment in the NTD group compared to controls, while the atRA-treated group without NTDs showed no notable differences in growth. Immunohistochemistry (IHC) results demonstrated decreased NeuN and PCNA expression in the NTD group's spinal cord. Oxidative stress markers showed markedly reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity, alongside increased malondialdehyde (MDA) levels in the NTD group, indicating heightened oxidative stress. Analysis of apoptosis-related proteins revealed elevated Bax and caspase-3 levels, reduced Bcl-2 and lower poly (ADP-ribose) polymerase (PARP) in the NTD group, suggesting a pronounced shift towards proapoptotic pathways, potentially contributing to NTD progression. Our findings indicate that oxidative stress and apoptosis play significant roles in the development of NTDs. Future investigations should aim to pinpoint critical regulatory genes or proteins that might be targeted for therapeutic interventions to alleviate oxidative stress and apoptosis in NTD development.

神经管缺陷(NTDs)是严重的先天性异常,严重影响中枢神经系统,由胚胎早期神经管未能关闭引起。在这项研究中,我们研究了暴露于全反式维甲酸(atRA)后的胎儿大鼠的NTDs和相关的病理生理机制。在实验组15只怀孕大鼠的168个胚胎中,78%显示NTDs伴有明显的脊柱畸形,主要发生在腰骶区,与人类病例相似。体重和冠臀长(CRL)测量显示,与对照组相比,NTD组的生长明显受损,而没有NTD的atra治疗组的生长没有显着差异。免疫组化(IHC)结果显示NTD组脊髓NeuN和PCNA表达降低。氧化应激标志物显示,NTD组超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-px)活性显著降低,丙二醛(MDA)水平升高,表明氧化应激升高。凋亡相关蛋白分析显示,NTD组中Bax和caspase-3水平升高,Bcl-2和聚(adp -核糖)聚合酶(PARP)水平降低,提示向促凋亡途径的明显转变,可能导致NTD进展。我们的研究结果表明,氧化应激和细胞凋亡在NTDs的发展中起重要作用。未来的研究应旨在确定关键的调控基因或蛋白,这些基因或蛋白可能针对治疗干预,以减轻NTD发展过程中的氧化应激和细胞凋亡。
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引用次数: 0
Ascorbic acid supplementation in adolescent rats ameliorates anxiety-like and depressive-like manifestations of nicotine-ethanol abstinence: Role of oxidative stress, inflammatory, and serotonergic mechanisms 在青春期大鼠中补充抗坏血酸可改善尼古丁-乙醇戒断的焦虑样和抑郁样表现:氧化应激、炎症和血清素能机制的作用
IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY Pub Date : 2024-12-04 DOI: 10.1002/jdn.10392
Alireza Najafzadeh, Mobina Mahdizadeh, Samaneh Kakhki, Ali Rahimi, S. Mohammad Ahmadi-Soleimani, Farimah Beheshti

Background

The present study aims to assess the therapeutic potential of vitamin C (Vit C) on anxiety- and depressive-like behavior induced by abstinence from chronic nicotine-ethanol co-exposure in adolescent male rats.

Materials and methods

Adolescent male rats were divided into seven experimental groups with ten rats as follows: 1) vehicle, 2) Nicotine (Nic)-Ethanol (Eth): received Nic (2 mg/kg) and Eth (20%) in drinking water from 21 to 42 days of age, 3–5) Nic-Eth-Vit C 100/200/400: received Nic and Eth from 21 to 42 days of age and received Vit C 100/200/400 mg/kg from 43 to 63 days of age, 6) Nic-Eth-Bupropion (Bup)- Naloxone (Nal): received Nic and Eth from 21 to 42 days of age and received Bup and Nal from 43 to 63 days of age, and 7) Vit C 400 mg/kg: received Vit C 400 mg/kg from 43 to 63 days of age. Behavioral assessments were done by elevated plus maze (EPM), forced swimming test (FST), marble burring test (MBT), and open field tests (OFT). Furthermore, specific biochemical variables associated with oxidative, inflammatory, and serotonergic profiles were quantified.

Results

According to the obtained results, Nic and Eth induced anxiety and depression in treated rats. We showed that two higher doses of Vit C increases the active struggling time in FST and decreases both the time spent in the peripheral zone of OFT and the time spent in the closed arms of EPM. In addition, animals treated by Vit C buried less number of marbles in MBT compared to their control counterparts. Nic and Eth induced oxidative stress and inflammation in cortical tissues of treated rats. Biochemical parameters were improved in the Nic-Eth group receiving Vit C 200/400 mg/kg and Bup-Nal through establishing a balance between oxidant/anti-oxidant and inflammatory/anti-inflammatory mediators. In addition, serotonin level was increased, while Monoamine oxidase (MAO) activity was notably decreased.

Conclusion

The present findings support the beneficial effect of Vit C on anxiety- and depressive-like behavior induced by Nic-Eth withdrawal through various mechanisms such as the promotion of antioxidant defense, suppression of inflammatory mediators, and enhancement of serotoninergic function.

背景:本研究旨在评估维生素C (Vit C)对青春期雄性大鼠慢性尼古丁-乙醇共暴露戒断引起的焦虑和抑郁样行为的治疗潜力。材料与方法:将青春期雄性大鼠分为7个实验组,每组10只:1)载药,2)尼古丁(Nic)-乙醇(Eth): 21 ~ 42日龄在饮用水中给予Nic (2 mg/kg)和Eth (20%), 3 ~ 5) Nic-Eth-Vit C 100/200/400: 21 ~ 42日龄给予Nic和Eth, 43 ~ 63日龄给予Vit C 100/200/400 mg/kg, 6) Nic-Eth-安非他酮(Bup)-纳洛酮(Nal)。21 ~ 42日龄给予Nic和Eth, 43 ~ 63日龄给予Bup和Nal; 7)维生素C 400 mg/kg: 43 ~ 63日龄给予维生素C 400 mg/kg。行为学评估采用高架迷宫(EPM)、强迫游泳测试(FST)、大理石毛刺测试(MBT)和野外测试(OFT)。此外,与氧化、炎症和血清素能谱相关的特定生化变量被量化。结果:根据所得结果,Nic和Eth可引起大鼠焦虑和抑郁。我们发现,两个较高剂量的Vit C增加了FST的活跃挣扎时间,减少了OFT外围区和EPM闭合臂的时间。此外,与对照组相比,Vit C处理过的动物在MBT中埋下的弹珠数量更少。Nic和Eth诱导大鼠皮质组织氧化应激和炎症反应。通过在氧化/抗氧化和炎症/抗炎介质之间建立平衡,维生素C 200/400 mg/kg和Bup-Nal给予Nic-Eth组的生化指标得到改善。血清素水平升高,单胺氧化酶(MAO)活性显著降低。结论:本研究结果支持维生素C对Nic-Eth戒断所致的焦虑和抑郁样行为的有益作用,其机制包括促进抗氧化防御、抑制炎症介质和增强血清素能功能。
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引用次数: 0
期刊
International Journal of Developmental Neuroscience
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