Zinc transporter‐1: a novel NMDA receptor‐binding protein at the postsynaptic density

Zinc (Zn²⁺) is believed to play a relevant role in the physiology and pathophysiology of the brain. Hence, Zn²⁺ homeostasis is critical and involves different classes of molecules, including Zn²⁺ transporters. The ubiquitous Zn²⁺ transporter‐1 (ZNT‐1) is a transmembrane protein that pumps cytosolic Zn²⁺ to the extracellular space, but its function in the central nervous system is not fully understood. Here, we show that ZNT‐1 interacts with GluN2A‐containing NMDA receptors, suggesting a role for this transporter at the excitatory glutamatergic synapse. First, we found that ZNT‐1 is highly expressed at the hippocampal postsynaptic density (PSD) where NMDA receptors are enriched. Two‐hybrid screening, coimmunoprecipitation experiments and clustering assay in COS‐7 cells demonstrated that ZNT‐1 specifically binds the GluN2A subunit of the NMDA receptor. GluN2A deletion mutants and pull‐down assays indicated GluN2A(1390–1464) domain as necessary for the binding to ZNT‐1. Most importantly, ZNT‐1/GluN2A complex was proved to be dynamic, since it was regulated by induction of synaptic plasticity. Finally, modulation of ZNT‐1 expression in hippocampal neurons determined a significant change in dendritic spine morphology, PSD‐95 clusters and GluN2A surface levels, supporting the involvement of ZNT‐1 in the dynamics of excitatory PSD.

     

胸腰段骨折外科治疗的研究进展

胸腰椎骨折是骨科临床工作中常见的损伤。胸腰段骨折往往伴发不同程度的脊髓损伤,很大程度上影响患者的生活质量。准确把握其分型,并制定恰当、及时、有效的治疗方案,对伤员进行救治,恢复椎体的高度、序列与曲度,解除神经压迫,重建脊柱稳定性,减少近远期并发症,改善预后有着深远的意义。本文通过对胸腰段骨折的分类、手术入路、手术方式、不同类型骨折的治疗等四个方面的国内外近期研究成果作一综述。     

Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual-energy X-ray absorptiometry technique

doi: 10.1111/j.1741‐2358.2012.00625.x Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual‐energy X‐ray absorptiometry technique Objective: The aim of this study was to compare the mandibular body bone mineral density according to bone mineral density status of spine and femur measured by dual‐energy X‐ray absorptiometry (DXA) technique in elderly edentulous individuals. Background: One of the factors that affect the survival rate of implants is bone mineral density (BMD) of the jaws. Materials and methods: Fifty edentulous elderly patients’ (27 women and 23 men) spine, femur and the mandibular body BMDs were measured using DXA technique. BMD scans of the AP lumbar spine (L2–L3) and femur were classified using World Health Organisation criteria for bone mass. Results: There was a statistically significant difference between the normal femur group’s–osteoporosis group’s mandibular body BMD (p = 0.001) and femoral osteopaenia group’s–osteoporosis group’s mandibular body BMD (p < 0.001). The femoral osteoporosis group’s mandibular body BMDs were lower than those of both the normal femoral and the femoral osteopaenia group subjects’. Conclusion: Classification of edentulous mandibles according to low and high bone mineral densities is a problem in implant dentistry. The results of this study demonstrated that femoral bone mineral density status may be used to provide preliminary information about the bone mineral density of the mandibular body region in elderly edentulous subjects.     

From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation

Both Neurofibromatosis type I (NF1) and inclusion body myopathy with Paget''s disease of bone and frontotemporal dementia (IBMPFD) are autosomal dominant genetic disorders. These two diseases are fully penetrant but with high heterogeneity in phenotypes, suggesting the involvement of genetic modifiers in modulating patients'' phenotypes. Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. Both NF1 and VCP/p97 are critical for dendritic spine formation, which provides the cellular mechanism explaining the cognitive deficits and dementia found in patients. Moreover, disruption of the interaction between neurofibromin and VCP impairs dendritic spinogenesis. Neurofibromin likely influences multiple downstream pathways to control dendritic spinogenesis. One is to activate the protein kinase A pathway to initiate dendritic spine formation; another is to regulate the synaptic distribution of VCP and control the activity of VCP in dendritic spinogenesis. Since neurofibromin and VCP/p97 also regulate cell growth and bone metabolism, the understanding of neurofibromin and VCP/p97 in neurons may be applied to study of cancer and bone. Statin treatment rescues the spine defects caused by VCP deficiency, suggesting the potential role of statin in clinical treatment for these two diseases.     

Neonatal fluoxetine exposure alters motor performances of adolescent rats

Growing evidence from human and animal studies has shown adverse consequences of maternal usage of antidepressants in their newborn babies. To study the effects of early antidepressant exposure on motor function later in life, we treated neonatal rat pups with fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI)-type antidepressant, from the day of birth to postnatal day 4 and examined motor performance during adolescence. FLX-treated rats had reduced locomotor activities in an open field and poorer motor performance on an accelerating rotarod compared to the control group of saline-treated animals. Nevertheless, the poorer motor performance largely improved after repetitive practices. To elucidate the structural alterations in the motor system, we examined the structure of neurons in motor-related brain regions. The shape, density, and soma size of cerebellar Purkinje cells were comparable in the two groups, however, density of dendritic spine in medial spiny neurons of striatum and Layer 5 pyramidal neurons in the primary motor cortex (M1) were reduced in FLX-rats. Furthermore, the basilar dendrites in M1 Layer 5 neurons had reduced dendritic complexity than those of the control animals. The impaired dendritic structure in striatal and cortical neurons in FLX-treated rats might account for their poorer motor performances. Together, the structure and function of the motor system are affected by early FLX exposure, the long-term effects of early exposure to SSRI-type antidepressants should be concerned.     

Tegumental ultrastructure of adult Gynaecotyla squatarolae (Digenea: Microphallidae)

Gynaecotyla squatarolae (Digenea: Microphallidae) adult flukes were recovered from experimental chicks at day 4-6 post-infection and their tegumental ultrastructure was observed with a scanning electron microscopy. They were pyriform in shape, and their anterior halves were concaved ventrally. The whole body surface was covered with tegumental spines, which were wide and 16-17 digitated between oral and ventral suckers. The density of spines and number of digits decreased posteriorly. The oral sucker was subterminal and the excretory pore was at the posterior end of the worm. Two ventral suckers were similar in appearance and protruded near midline of the worm. The genital atrium was dextral to the small ventral sucker. The dorsal surface was covered with tegumental spines, but the spines were sparser than on the ventral surface. On the middle portion of the dorsal surface, a small opening presumed to be the Laurer's canal was seen. From these findings, it has been confirmed that the adult G. squatarolae has unique characteristics in the surface ultrastructure.