Optical identification of calcium-dependent action potentials transiently expressed in the embryonic rat brainstem

Using multiple-site optical recording of transmembrane potential changes, we have found a new type of calcium-dependent action potential expressed transiently in the embryonic rat dorsal motor nucleus of the vagus nerve. Slice preparations with vagus nerve fibers attached were dissected from 12- to 16-day-old embryonic (E12–E16) rat brainstems, and they were stained with a voltage-sensitive merocyanine–rhodanine dye (NK2761). Electrical activities in response to vagal stimuli were optically recorded simultaneously from many sites using 1020- or 128-element photodiode array measuring systems. In brainstem preparations, two types of action potential-related optical signals were identified. One was detected from the dorsolateral region, and was related to sensory nerve activity (Type I). The other was detected from the dorsomedial region, and corresponded to the action potential in the dorsal motor nucleus of the vagus nerve (Type II). We found a difference in the ionic basis of the Type I vs Type II signals. The Type I signal was not altered in Ca²⁺-free bathing solution and was eliminated by tetrodotoxin, suggesting that the sensory nerve activity is mediated by Na⁺ currents. The Type II signal at early developmental stages (E12–E13, and some preparations in E14) was also independent of Ca²⁺. However, the Type II signal in later developmental stages (E15–E16, and some preparations in E14) did depend upon Ca²⁺: it was eliminated in Ca²⁺-free Ringer's solution, blocked by Cd²⁺, Ni²⁺ or Mn²⁺, and elicited in Sr²⁺-containing Ringer's solution, where CaCl₂ was replaced with SrCl₂. These results suggest that the cation which dominates the motoneuron action potential changes from Na⁺ to Ca²⁺ during development, and this change occurs around E14. With pharmacological analysis using Ca²⁺ channel blockers, we show that the Ca²⁺ channel mediating the motoneuron action potential is distinct from T-, L-, N-, P- or Q-type channels.

Because the vagal action potential in adult mammals is mainly mediated by Na⁺, we suggest that a Ca²⁺ action potential mediated by a new type of Ca²⁺ channel is expressed transiently in the rat dorsal motor nucleus of the vagus nerve at particular stages of development.     

Glucocorticoid production in the chicken bursa and thymus

Glucocorticoid (GC) hormones play an important role in thymic T cell selection and in the development of autoimmune diseases. Previous studies have shown that the mammalian thymus itself is able to produce GC. In order to assess the importance of these findings in terms of the evolutionary development of the immune system, we investigated the functional presence of steroidogenic enzymes in primary lymphoid organs of chickens, which represent one of the best studied non-mammalian species. To this end, we attempted to demonstrate enzyme activities of the whole set of steroidogenic enzymes for the synthesis of GC in the bursa of Fabricius and the thymus. We isolated steroidogenic organelles from primary lymphoid tissues, incubated these with radioactive (precursor) steroids in vitro and visualized the resulting products by thin-layer chromatography. Our results show that the chicken bursa as well as the chicken thymus possesses all enzymes and cofactors required for GC production. The observation of GC production in an organ responsible for B cell selection and maturation is a further step in uncovering the yet ill-defined mechanism of B cell selection. These results provide the biochemical basis for the in situ hormonal effects, and underline the general importance of GC hormones on T and B lymphocyte development and selection.     

Developmental trajectories in early hematopoiesis

The paths that hematopoietic stem cells take to develop from multipotent, self-renewing cells into committed lymphocytes has been a topic of debate for some time. During early hematopoiesis, multiple branchpoints have been described in which progeny cells segregate into cell lineages with distinct developmental potentials. In this issue of Genes & Development, Inlay and colleagues (pp. 2376–2381) identify novel intermediate stages through which hematopoietic progenitor cells travel.     

A primer on investigating the role of the microbiome in brain and cognitive development

Incorporating information regarding the gut microbiota into psychobiological research promises to shed new light on how individual differences in brain and cognitive development emerge. However, the investigation of the gut-brain axis in development is still in its infancy and poses several challenges, including data analysis. Considering that the gut microbiome is an eco-system containing millions of bacteria, one needs to utilize a breadth of methodologies and data analytic techniques. The present review serves two purposes. First, this review will inform developmental psychobiology researchers about the emerging study of the gut-brain axis in development and second, this review will propose methodologies and data analytic strategies for integrating microbiome data in developmental research.     

Developmental screening tests in achondroplastic children

Data on psychomotor de development are compiled on 197 achondroplastic children. The data are plotted in a manner similar to that used in the Denver Developmental Screening Test. Gross motor development is delayed in achondroplastic children as compared to children of approriate age. There is no difference in language development.     

A cyclin-like protein,ClgA, regulates development in Aspergillus nidulans

A cyclin-like protein from Aspergillus nidulans, ClgA, was identified. Its cyclin-like subunit shares 28.3% identity to Saccharomyces cerevisiae Clg1. Deletion of clgA slightly influenced fungal growth, but repressed asexual development and made it more sensitive to temperature variations. It also downregulated expression of brlA, abaA and wetA, which are critically responsible for asexual development. Sexual development was impaired in the ΔclgA mutant. Its related genes, veA and nosA, were expressed weakly in the ΔclgA mutant, while nsdD expression showed the opposite behavior. Generally, ClgA functioned differently from other reported cyclins in development of A. nidulans.     

Topography and structure of vasculature in developing cortex of rat kidney

Summary Young Wistar and SIV rats fixed by retrograde vascular perfusion were used for scanning and transmission electron microscopic, as well as light microscopic observations of the developing renal cortex and its vasculature. The latter was additionally observed by scanning electron microscopy of vascular casts effectuated by injection of methacrylate into the renal blood vessels.Disappearance of the initial nephron anlages — the vesicles — took place in the observed animals 2–3 days after birth, and another 2–3 days later the S-shaped bodies with the developing glomeruli differentiated into more advanced nephrons. The vascular system in the developing renal cortex consists of arterial supplying vessels, the sinusoid-like capillaries, and, continuous with the latter, large vessels which terminate in the arcuate vein. The arterial vessels assume their adult pattern already in the differentiating kidney, except their terminal — peripheral branching which is represented by arterial capillaries continuous with the drainage system. When nephronogenesis terminates the arterial capillaries are transformed into the young afferent vessels and the peripheral plexus of sinusoid-like capillaries receives its blood supply from the young efferent vessels. The sinusoid-like capillaries and large vessels give origin to the peritubular network of capillaries in the adult kidney, although their differentiation continues once nephronogenesis has been accomplished. They show some ultrastructural characteristics similar to those observed in sinusoids of other organs and they also differentiate in the same manner, by a conformation to the growing tubules.This work is dedicated to Professor Otto Bucher, M.D. (Lausanne), in honour of his 65th birthdayThe author wishes to thank Mrs. Madeleine Wirth and Miss Solange Gros for their excellent technical assistance     

Age-related differences in the chronic and acute response to cocaine in the rat

Behavioral sensitization is known to occur in adult animals after the chronic intermittent administration of cocaine. Dopaminergic pathways in the brain, such as the nigrostriatal and mesoaccumbens projections play a vital role in this phenomenon. These pathways are rudimentary in the 1st week of life, indicating that the developing animal may be unable to respond to cocaine in the same manner as an adult. In the present study, we report that the acute response to cocaine is remarkably similar between week-old and adult rats. Pups do not, however, show locomotor sensitization to acute cocaine after chronic cocaine administration as adults. © 1996 John Wiley & Sons, Inc.     

Apoptosis in the cortex of the developing mouse kidney

Published levels of apoptosis in developing rat kidney (approximately 2.5%) seem large for a tissue with no obvious need for continual cell death. This paper examines the levels and patterns of apoptosis and mitosis in the cortical region of the developing metanephros of the mouse, the standard mammalian model embryo. Using confocal microscopy on specimens stained with propidium iodide to highlight nuclear morphology, optical sections of wholemount kidneys to a depth of approximately 50 microm were analysed and mitotic, apoptotic and interphase nuclei counted in the various compartments. Of the approximately 200 000 cells examined over E11.5-16.5, 2-3% were mitotic, confirming observations based on cryosections; the mitotic index peaked at E14.5, dropping to approximately 0.5% by P14. The mean apoptotic index during this period was 0.28%; this figure from wholemounts was approximately 10% of that earlier reported in cryosectioned rat kidneys. One possible explanation for the difference is that cryosectioning turns out to create small nuclear fragments that can stain strongly with propidium. Such fragments are not seen in wholemounts and do not stain with TUNEL. Wholemount mouse E11.5 tails and E16.5 lungs were also analysed and both their mitotic and their apoptotic indexes were similar to those in wholemount developing kidneys. These results show that the level of apoptosis in wholemount embryonic mouse kidney cortex is far less than previously reported in cryosectioned rat embryonic kidneys, and typical of that in other mouse embryonic tissues whose development seems not to require apoptosis.     

Differential FSH exposure in preantral follicle culture has marked effects on folliculogenesis and oocyte developmental competence

BACKGROUND: We investigated at what stage early cultured preantral mouse follicles become dependent on a minimal effective FSH dose (10 mIU/ml) and analysed the influence of implementing FSH at several time-points during in vitro culture. METHODS: Two-layered mouse follicles were cultured for 12 days under seven different FSH exposure regimens and ovulated on day 13 by hCG/EGF. Ovulated cumulus-oocyte complexes were fertilized and embryos were cultured up to the blastocyst stage. RESULTS: When FSH was absent or added only once at the start of culture, follicle survival was significantly reduced (22 and 52% respectively versus 95% when FSH was continuously present, P < 0.01) and oocyte quality was compromised, providing few oocytes for embryo culture (19 and 7% versus 71% in continuous presence of FSH, P < 0.01). Optimal follicle survival rates can be ensured by implementing FSH at the latest from day 4 of culture. By introducing FSH later than day 4, follicle survival rates and number of ovulated oocytes decreased. Estradiol production and luteinization were strongly related to the moment of introducing FSH in culture. Fertilization and preimplantation embryo development rate were found to be highest in cultures where FSH support was implemented during the preantral stage. CONCLUSION: Exposure to FSH before formation of the antral-like cavity had a positive effect on follicle survival and oocyte robustness.     

补锌对婴幼儿智力及运动发育影响的Meta分析

目的评价补锌对婴幼儿运动和智力发育改善的作用。方法检索PubMed、EMBASE、Cochrane图书馆、中国期刊全文数据库、维普中文科技期刊数据库和万方数据库等,获得补锌对婴幼儿运动和智力发育影响的RCT文献。根据随机分配方法,分配隐藏,对研究对象、治疗方案和研究结果测量者采用盲法,结果数据的完整性,选择性报告研究结果,其他偏倚来源进行文献偏倚评估。以生后6～36个月智力发育指数（MDI）、运动发育指数（PDI）和发育商（DQ）为疗效判定指标。采用RevMan5.0软件进行Meta分析,检验异质性,根据异质性结果进行原因分析,并选择相应的效应模型分析。计量资料以SMD或WMD及其95%CI表示。结果①共检索到文献84篇,共10篇RCT满足纳入条件进入Meta分析。7篇文献采用了正确的随机方法,8篇文献采用了分配隐藏,9篇文献对受试者采用了盲法,8篇文献对研究者和结局测量者采用了盲法,9篇文献提及报道数据的完整性,9篇文献未选择性报告研究结果,仅1篇文献报道了其他偏倚来源。漏斗图检验未见显著发表偏倚。②Meta分析结果显示,补锌组与对照组MDI的差异无统计学意义,WMD=-0.08（95%CI：-1.55～1.40）;补锌组与对照组PDI的差异无统计学意义,SMD=0.15（95%CI：-0.12～0.42）。但研究间均具显著统计学异质性,根据补锌的剂量、是否与其他营养物质合用、纳入对象的营养状况行亚组分析,进一步探讨异质性产生的原因。亚组分析显示不能完全消除文献间的异质性,异质性可能还与其他因素有关。③补锌组与对照组DQ评分的差异无统计学意义,WMD=-0.72（95%CI：-7.97～6.53）。补锌组与对照组干预前后Alberta运动指数的差异无统计学意义,WMD=0.30（95%CI：-2.09～2.69）。结论早期补锌并未提高MDI、PDI及DQ评分,对婴幼儿运动和智力发育未显示有改善作用。鉴于研究间存在显著的统计学异质性,结论仍需谨慎看待。     

Age-related characteristics of brain development in children living in the north

The morphofunctional age-related development of the brain was studied in schoolchildren living in the difficult climatological-geographic and socioeconomic conditions of the north (Arkhangel’sk region). Of the 62 students in country middle schools, EEG amplitude-frequency, time, and spatial measures corresponded to age norms (European norms) in only 10 cases (16%). A further 26 children (53%) showed minor abnormalities in the form of an inadequate degree of organization of the temporospatial EEG pattern, mainly in the frontal and temporal lobes of the brain, with increases in the levels of the theta and delta rhythms, and the absence of any marked “functional nucleus” in the alpha rhythm. In the remaining 14 children (29%), EEG measures showed more marked delays in mental development (DMD), which were combined with learning difficulties and abnormal behavior. The retardation in the morphofunctional development of the brain in northern children averaged 1.5–2 years, which coincides with delays in hormonal and physical development described by other authors. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 7, pp. 729–739, July, 2005.     

性发育疾病新的分类和基因诊断

性发育疾病(Disorders of sex development,DSD)是性决定和性分化异常的一组异质性遗传病,是由于染色体畸变或单基因突变导致的性发育遗传和内分泌途径的改变。曾经用雌雄间体、假两性畸形、真两性畸形和性反转这些术语用于描述性发育疾病,但有轻蔑含义。2006年欧洲儿科内分泌协会(European Society for Pardiatric Endocrinology,ESPE)和Lawson Wilkins儿科内分泌协会(Lawson Wilkins Pardiatric Endocrine Society,LWPES)联合召开了由内分泌学家、外科学家、遗传学家、心理学家和患者支持小组成员参加的会议,提出了新的术语、分类标准和已知的突变基因。在此,与大家共同探讨。     

水通道蛋白在鼠肺发育过程中的变化及意义

目的： 探讨水通道蛋白（AQPs）mRNA及蛋白表达在鼠肺发育过程中的变化及意义。方法: 以胎鼠、新生鼠、幼鼠和成年大鼠为研究对象,采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学（SABC）方法分别检测几种主要水通道AQP1、AQP3、AQP4和AQP5 mRNA及蛋白在肺脏的表达和分布;同时测定肺发育过程中一些相关指标,进行对比分析。结果: 大鼠肺发育连续不断,从胎鼠至新生鼠期增长最快,以后增速减慢,为一个动态的过程。肺AQPs mRNA在胎鼠时均开始微量转录,仅出现AQP1蛋白表达,出生后AQPs mRNA及蛋白均快速增加,呈增量表达至成年期。相关性分析显示,AQPs变化与肺发育指标变化存在显著正相关（P<0.05）。结论: AQPs可能参与了大鼠肺发育的诸多重要生理过程。     

X-chromosome polysomy in the female: personal experience and review of the literature

The mental, physical and sexual development of 15 triple-, four tetra-, and one penta-X patients is described and the most important data on this subject are reviewed.     

儿童脑发育及神经发育障碍的多模态MRI研究进展

目的 总结多模态MRI技术在儿童脑发育及神经发育障碍（NDDs）中的应用研究进展。方法 在中国知网、万方数据、PubMed及Web of Science 等中英文数据库,以“儿童脑发育”“神经发育障碍”“磁共振成像”以及“brain development” “neurodevelopmental disorders” “children” “MRI”等为关键词,检索1999年1月—2021年1月有关脑发育及NDDs疾病的MRI研究的相关文献,共检索到7 974篇文献,排除内容不相符、无法获取全文、质量较低、证据等级不高、重复研究的文献,最终纳入49篇英文文献,对其进行总结、分析。结果 多模态脑影像学技术（如形态学、解剖学及功能MRI）结合当前机器学习分析技术（如脑年龄预测）和影像遗传学技术,从结构到功能、从局域到网络性质,描绘了正常和异常儿童脑发育的轨迹,促进了对NDDs病理生理机制的理解。结论 结合定量化分析的多模态MRI技术,可用于对NDDs疾病的大脑结构及功能改变进行观察和对NDDs疾病机制的研究,并提供影像生物标志物,在儿童脑发育及NDDs疾病的早期诊断、分类和预后方面具有较高的应用价值。