Maturation of membrane properties of neurons in the rat deep cerebellar nuclei

Patch clamp recordings of neurons in the adult rat deep cerebellar nuclei have been limited by the availability of viable brain slices. Using a new slicing technique, this study was designed to explore the maturation of membrane properties of neurons in the deep cerebellar nuclei (DCN)—an area involved in rat eyeblink conditioning. Compared to whole‐cell current–clamp recordings in DCN in rat pups at postnatal day 16 (P16) to P21, recordings from weanling rats at P22–P40 revealed a number of significant changes including an increase in the amplitude of the afterhyperpolarization (AHP)—an index of membrane excitability which has been shown to be important for eyeblink conditioning—a prolonged interval between the first and second evoked action potential, and an increase in AHP amplitude for hyperpolarization‐induced rebound spikes. This is the first report of developmental changes in membrane properties of DCN which may contribute to the ontogeny of eyeblink conditioning in the rat. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1268–1276, 2014     

电刺激猫小脑顶核对动脉血压和肾交感神经放电的影响

在38只麻醉及人工呼吸的猫,观察到电刺激小脑顶核嘴侧部能引起动脉血压显著升高;肾交感神经放电于刺激期间显著增加。去缓冲神经对刺激顶核所引起的血压反应的幅度和肾交感神经放电均无明显影响,但可明显延长血压反应升高相以及血压恢复期的时间。静脉注射氯庄定引起血压降低、心率减慢及肾交感神经放电的抑制,并能减弱刺激顶核引起的血压反应,但增强了刺激顶核引起的肾神经放电的变化。电解损毁延髓腹外侧面引起血压降低及肾交感神经放电的抑制,然而无论单侧还是双侧损毁延髓腹外侧面都不能阻断刺激顶核所引起的血压和肾交感神经放电的反应。以上结果表明,电刺激顶核能引起明显的心血管反应,其反应的下行性通路可能不通过延髓腹外侧面。     

Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis

Lack of Sonic hedgehog (Shh) signaling, mediated by the Gli proteins, leads to severe pulmonary hypoplasia. However, the precise role of Gli genes in lung development is not well established. We show Shh signaling prevents Gli3 proteolysis to generate its repressor forms (Gli3R) in the developing murine lung. In Shh(-/-) or cyclopamine-treated wild-type (WT) lung, we found that Gli3R level is elevated, and this upregulation appears to contribute to defects in proliferation and differentiation observed in the Shh(-/-) mesenchyme, where Gli3 is normally expressed. In agreement, we found Shh(-/-);Gli3(-/-) lungs exhibit enhanced growth potential. Vasculogenesis is also enhanced; in contrast, bronchial myogenesis remains absent in Shh(-/-);Gli3(-/-) compared with Shh(-/-) lungs. Genes upregulated in Shh(-/-);Gli3(-/-) relative to Shh(-/-) lung include Wnt2 and, surprisingly, Foxf1 whose expression has been reported to be Shh-dependent. Cyclins D1, D2, and D3 antibody labelings also reveal distinct expression patterns in the normal and mutant lungs. We found significant repression of Tbx2 and Tbx3, both linked to inhibition of cellular senescence, in Shh(-/-) and partial derepression in Shh(-/-); Gli3(-/-) lungs, while Tbx4 and Tbx5 expressions are less affected in the mutants. Our findings shed light on the role of Shh signaling on Gli3 processing in lung growth and differentiation by regulating several critical genes.     

小脑皮层在兔瞬膜条件反射过程中的调制作用

以音调结合气流刺激兔角膜的训练建立瞬膜条件反射,在条件反射率刚达90%,连续出现三组的学习初始阶段,电解损毁小脑半球第六小叶皮层使 D-I 核的学习相关性电活动和瞬膜条件反射消除,但不影响“非条件”反射,而在经一周巩固训练的动物,损毁小脑皮层上述区域不发生影响。D-I 核的细胞自发电活动在学习初期和记忆巩固时期也有所不同。在学习后期,D-I 核的细胞自发电活动频率减低,和在学习初期与损毁小脑皮层后的频率变化相似。实验结果表明:在瞬膜条件反射过程中,以小脑皮层为主导,对瞬膜条件反射的产生和D-I 核的学习相关性电活动具有调制作用。随着记忆巩固过程,D-I 核脱离皮层的控制而发展成为这一学习模式的记忆痕迹基础部位。     

组胺对大鼠小脑皮层浦肯野细胞的兴奋作用

在离体大鼠小脑脑片上观察了组胺对小脑皮层第Ⅹ小叶浦肯野细胞的作用。组胺（３～１００μｍｏｌ／Ｌ）主要引起浦肯野细胞的兴奋反应（９４４％,５１／５４）,在少数细胞上也观察到组胺所引起的放电抑制现象（５６％,３／５４）。用低Ｃａ２＋／高Ｍｇ２＋人工脑脊液灌流脑片,不能取消浦肯野细胞对组胺的兴奋反应（ｎ＝４）。Ｈ２受体对抗剂ｒａｎｉｔｉｄｉｎｅ（０１～５μｍｏｌ／Ｌ）能够阻断浦肯野细胞对组胺的兴奋反应（ｎ＝２０）,而Ｈ１受体对抗剂ｔｒｉｐｒｏｌｉｄｉｎｅ（０５～５μｍｏｌ／Ｌ）不能够（ｎ＝９）或仅轻微地（ｎ＝４）阻断浦肯野细胞对组胺的兴奋反应。这些结果提示,组胺可能主要通过Ｈ２受体的介导对浦肯野细胞起兴奋性调节作用,下丘脑小脑组胺能神经通路可能参与了小脑的某些躯体的和非躯体的功能调节。     

Post-translational modifications in MeHg-induced neurotoxicity

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.     

白介素-6对NMDA诱导的小脑神经元放电活动的抑制作用及其机制

目的：观察白介素-6（IL-6）对N-甲基-D-天冬氨酸（NMDA）激发的神经元放电活动的影响及其可能的作用机制。方法：用含IL-6、NMDA和JAK抑制剂ACA90的人工脑脊液（ACSF）灌流小脑脑片,利用离体脑片神经元单位放电细胞外记录技术,记录药物对小脑间位核神经元放电的影响。用Western blot法测定间位核神经元NMDA受体亚单位1（NRI）的磷酸化水平。结果：单独用12．5μmol／L和25μmol／LNMDA灌流,神经元放电频率均较基础放电频率增加;用不同浓度IL-6（50,100,200μg／ml）联合NMDA作用后,神经尤的放电频率出现浓度依赖性地降低;AG490可部分阻断IL-6对NMDA兴奋神经元放电的抑制作用。与单独NMDA处理组比较,用IL-6联合NMDA处理神经元后,神经元的NR1磷酸化水平出现浓度依赖性地降低。AG490可阻断IL-6所致的神经元NR1磷酸化水平的降低。结论：IL-6可抑制NMDA激发的小脑间位核神经元的放电兴奋活动;并同时下调神经元的NR1磷酸化水平。     

Factors affecting the distribution of enamel hypoplasias within the human permanent dentition

Frequencies and morphological and chronological distributions of enamel hypoplasias are presented by tooth type (permanent I1 to M2s), based on a sample of 30 prehistoric Amerindians with complete and unworn dentitions. There is nearly a tenfold variation in frequency of defects by tooth, ranging from 0.13 per mandibular second molar to 1.27 per maxillary central incisor. The six anterior teeth average between 0.70 and 1.27 defects/tooth, whereas the eight posterior teeth average between 0.43 and 0.13 defects/tooth. Earlier developing teeth, such as incisors, have earlier peak frequencies of defects (2.0-2.5 years), while later developing teeth, such as second molars, have subsequent peak frequencies (5.0-6.0 years). These variations are relevant when comparing hypoplasia data based on different teeth. Differences in hypoplasia frequencies among teeth are not solely due to variation in time of crown development, as is usually reported. Rather, there is evidence for biological gradients in susceptibility to ameloblastic disruption. Anterior teeth are more hypoplastic than posterior teeth. More developmentally stable "polar" teeth are more hypoplastic than surrounding teeth. Polar teeth may be more susceptible to hypoplasias because their developmental timing is less easily disrupted. In all teeth, hypoplasias are most common in the middle and cervical thirds. Crown development and morphological factors, such as enamel prism length and direction, may influence the development and expression of enamel surface defects.     

Case Report: A patient with spinocerebellar ataxia type 31 and sporadic Creutzfeldt-Jakob disease

We report a Japanese patient with spinocerebellar ataxia type 31 (SCA31) and sporadic Creutzfeldt-Jakob disease (sCJD). A 52-year-old man developed progressive cognitive impairment after the appearance of cerebellar symptoms. Brain MR diffusion-weighted imaging (DWI) demonstrated a slowly expanding hyperintense lesion in the cerebral cortex. The patient was finally diagnosed as having both SCA31 and sCJD by identification of genetic mutations and by real-time quaking-induced conversion (RT-QUIC) analysis of the cerebrospinal fluid (CSF), respectively. Here, we report the clinical details of this rare combined case, with particular reference to the association between prion protein and the early onset of SCA31.