Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis

Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate‐limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT‐mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self‐renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration.     

Marked differences in the number and type of synapses innervating the somata and primary dendrites of midbrain dopaminergic neurons,striatal cholinergic interneurons,and striatal spiny projection neurons in the rat

Elucidating the link between cellular activity and goal‐directed behavior requires a fuller understanding of the mechanisms underlying burst firing in midbrain dopaminergic neurons and those that suppress activity during aversive or non‐rewarding events. We have characterized the afferent synaptic connections onto these neurons in the rat substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and compared these findings with cholinergic interneurons and spiny projection neurons in the striatum. We found that the average absolute number of synapses was three to three and one‐half times greater onto the somata of dorsal striatal spiny projection neurons than onto the somata of dopaminergic neurons in the SNpc or dorsal striatal cholinergic interneurons. A similar comparison between populations of dopamine neurons revealed a two times greater number of somatic synapses on VTA dopaminergic neurons than SNpc dopaminergic neurons. The percentage of symmetrical, presumably inhibitory, synaptic inputs on somata was significantly higher on spiny projection neurons and cholinergic interneurons compared with SNpc dopaminergic neurons. Synaptic data on the primary dendrites yielded similar significant differences for the percentage of symmetrical synapses for VTA dopaminergic vs. striatal neurons. No differences in the absolute number or type of somatic synapses were evident for dopaminergic neurons in the SNpc of Wistar vs. Sprague‐Dawley rat strains. These data from identified neurons are pivotal for interpreting their electrophysiological responses to afferent activity and for generating realistic computer models of neuronal networks of striatal and midbrain dopaminergic function. J. Comp. Neurol. 524:1062–1080, 2016. © 2015 Wiley Periodicals, Inc.     

Developmental pattern of the neuronal intermediate filament inaa in the zebrafish retina

α‐Internexin is a member of the neuronal intermediate filament (nIF) protein family, which also includes peripherin and neurofilament (NF) triplet proteins. Previous studies found that expression of α‐internexin precedes that of the NF triplet proteins in mammals and suggested that α‐internexin plays a key role in the neuronal cytoskeleton network during development. In this study, we aimed to analyze the expression patterns and function of internexin neuronal intermediate filament protein‐alpha a (inaa), the encoding gene of which is a homolog of the mammalian α‐internexin, during retinal development in zebrafish. Via in vitro and in vivo studies, we demonstrated that zebrafish inaa is an α‐internexin homolog that shares characteristics with nIFs. An immunohistochemical analysis of zebrafish revealed that inaa was distributed dynamically in the developing retina. It was widely localized in retinal neuroepithelial cells at 1 day postfertilization (dpf), and was mainly found in the ganglion cell layer (GCL) and inner part of the inner nuclear layer (INL) from 3–9 dpf; after 14 dpf, it was restricted to the outer nuclear layer (ONL). Moreover, we demonstrated for the first time that inaa acted distinctively from the cytoskeletal scaffold of zebrafish cone photoreceptors during development. In conclusion, we demonstrated the morphological features of a novel nIF, inaa, and illustrated its developmental expression pattern in the zebrafish retina. J. Comp. Neurol. 524:3810–3826, 2016. © 2016 Wiley Periodicals, Inc.     

老年陈旧性症状性骨质疏松性胸腰椎骨折后路长节段内固定术后近端交界性后凸的危险因素

目的:探讨后路长节段内固定治疗老年Ⅳ型陈旧性症状性骨质疏松性胸腰椎骨折（CSOTLF）后近端交界性后凸（PJK）发生的相关危险因素。方法:采用病例对照研究分析2013年1月至2018年6月西安交通大学附属红会医院收治的95例老年Ⅳ型CSOTLF患者临床资料,其中男32例,女63例;年龄60~85岁［（67.4±6.5）...     

模拟战时复苏策略对家兔失血性心跳骤停效果的初步观察

目的 观察模拟战时复苏策略救治失血性心跳骤停的初步效果.方法 本文为前瞻性研究.50只家兔[雌雄不拘,重量(2.6±0.4)kg,兔龄(8.9±0.4)个月]随机分为A～E 5组,每组10只.通过从股动脉置管中以2mL/(kg·min)的速度抽取血液,制备失血性心跳骤停模型.制模成功(收缩压<10mmHg,持续20s以...     

乳腺导管原位癌伴微浸润与导管原位癌的临床病理及X线表现对比分析

目的对比分析乳腺导管原位癌伴微浸润(DCISM)与导管原位癌(DCIS)的X线及临床病理表现及DCISM的预测因子。方法收集2016年1月至2020年7月在青岛大学附属医院经手术病理证实的DCISM及DCIS患者626例,患者术前均接受乳腺X摄影检查。参照乳腺影像报告和数据系统(BI-RADS)标准对DCISM与DCIS患者X线表现进行分类诊断。采用χ²检验或Fisher确切概率法分析DCISM与DCIS患者临床病理及X线表现的差异性,应用单因素和多因素二元logistic回归分析探讨与DCISM相关的危险因素。结果626例患者中,DCISM患者171例,DCIS患者455例。单因素回归分析表明,肿瘤直径≥2.7cm、高核级别、粉刺性坏死、淋巴结阳性、Ki67高表达、雌激素受体及孕激素受体阴性是DCISM的预测因子(P<0.05)。多因素回归分析显示,肿瘤直径≥2.7cm(OR 2.229,95%CI 1.505~3.301,P<0.001)、高核级别(OR 1.711,95%CI 1.018~2.875,P=0.043)、淋巴结阳性(OR 4.140,95%CI 1.342~12.773,P=0.013)是DCISM的独立预测因子(P<0.05)。乳腺X线摄影中,DCIS与DCISM患者的病变类型、有无钙化及钙化分布差异具有统计学意义(χ²分别为17.42、9.65、9.10,P<0.05),17.6%(80/455)的DCIS患者表现为隐匿性病变,49.1%(84/171)的DCISM表现为钙化伴肿块、非对称致密、结构扭曲。团簇状钙化多见于DCIS(41.5%,120/289),而区域性钙化在DCISM中更普遍(35.9%,47/131)。结论乳腺X线摄影表现为钙化性病变及区域性钙化在DCISM中更常见。肿瘤直径≥2.7cm、高核级别、淋巴结阳性是DCISM的独立预测因子。     

血浆外泌体源性miR-1224-5p与溃疡性结肠炎患者炎性反应状态及预后的关系

目的 探讨血浆外泌体源性miR-1224-5p与溃疡性结肠炎(ulcerative colitis,UC)患者炎性反应状态及预后的关系.方法 选择2018年1月-2019年10月海安市人民医院收治的103例UC患者,其中活动期57例,缓解期46例;选择同期来我院体检的60例健康人群作为对照组.采用实时荧光定量聚合酶链反...