Dexamethasone induces TrkA and p75NTR immunoreactivity in the cerebral cortex and hippocampus

Nerve growth factor (NGF) plays a crucial role in synaptic plasticity during brain development and adulthood by activating a dual receptor system composed of TrkA and p75 (p75NTR) receptors. Exogenous NGF modulates the expression of both receptors. Little is known about the ability of endogenous NGF to regulate the expression of these receptors in basal forebrain cholinergic terminals. The ability of glucocorticoids to increase NGF expression in the hippocampus prompted us to investigate whether the synthetic glucocorticoid dexamethasone (DEX) increases TrkA and p75NTR expression in NGF-target cholinergic neurons in developing rats. We first examined the effect of DEX on NGF mRNA by in situ hybridization. DEX given systemically (0.5 mg/kg, sc) for 1 week to 7-day-old rats elicited an increase in NGF mRNA levels in the dentate gyrus of the hippocampus and superficial layers II and III of the cerebral cortex. Immunohistochemical analysis of p75NTR and TrkA levels revealed a dramatic increase in p75NTR immunoreactivity (IR) in both basal forebrain and hippocampus and TrkA IR in the hippocampus. Interestingly, in DEX-treated rats more axonal terminals were immunopositive for p75NTR in the hippocampus and cortex, suggesting an increase in p75NTR IR in cell bodies as well as in terminals. Our data indicate that the endogenously produced NGF elicits biological changes similar to those of the exogenously delivered NGF. We suggest that glucocorticoids might regulate and coordinate cholinergic neuronal maturation by increasing the biosynthesis of NGF.     

神经生长因子脂质体大鼠鼻腔给药的药效学研究

 目的对神经生长因子(nerve growth factor,NGF)和NGF脂质体(NGF-SSL)鼻腔给药的药效学进行研究,并与NGF静脉给药相比较。方法鹅膏蕈氨酸(ibotenicacid,IBO)大鼠Meynert核注射制造阿尔茨海默氏病(alzheimer'sdisease,AD)模型,以生理盐水Meynert核注射作为假手术对照组,通过水迷宫试验,跳台实验和乙酰胆碱酯酶(AchE)组织化学染色来评价AD模型。并应用此模型采用同样方法研究NGF静脉给药,NGF和NGF-SSL鼻腔给药后的药效。结果AD模型经鉴定能够应用于药效研究。NGF鼻腔给药药效优于NGF静脉注射,NGF经脂质体包载后药效进一步提高。NGF-SSL鼻腔给药后能明显保护胆碱能神经元免受损伤,动物游泳时间缩短,跳台潜伏期延长,AchE染色积分光密度接近正常大鼠。结论鼻腔给药能够实现药物给药途径上的脑靶向,药物经脂质体包载后能明显增加其脑摄入,提高药效。     

Not all neurogenic bladders are the same: a proposal for a new neurogenic bladder classification system

Neurogenic bladder (NGB) has long been defined as a clinical entity that describes a heterogeneous collection of syndromes. The common theme is a bladder disorder concomitant with a neurologic disorder. This definition does not give the clinician much information about the bladder disorder, nor how to treat it, or even what the natural history of the disorder is likely to be. It may be time for a new classification scheme to better define the bladder defect and prognosis, as well as inform treatment. We propose a classification system based on seven categories, each having a neurologic defect in a distinct anatomic location. This is termed SALE (Stratify by Anatomic Location and Etiology). In addition, the presence or absence of bowel dysfunction and autonomic dysreflexia will be reported. In the future, as more definite prognostic information can be gleaned from biomarkers, we anticipate adding urinary nerve growth factor (NGF) and urinary brain-derived neurotrophic factor (BDNF) levels to the definition. We expect the SALE system to efficiently describe a patient suffering from NGB and simultaneously inform the most appropriate treatment, follow-up regimen, and long-term prognosis.     

Salidroside protects PC12 cells from MPP-induced apoptosis via activation of the PI3K/Akt pathway

Oxidative stress plays an important role in the pathogenesis of Parkinson’s disease (PD). Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., can exert potent antioxidant properties. In this study, we investigated the protective effects, and the possible mechanism of action, of SAL against 1-methyl-4-phenylpyridinium (MPP⁺)-induced cell damage in rat adrenal pheochromocytoma PC12 cells. Pretreatment of PC12 cells with SAL significantly reduced the ability of MPP⁺ to induce apoptosis in a dose and time-dependent manner. SAL significantly and dose-dependently inhibited MPP⁺-induced chromatin condensation and MPP⁺-induced release of lactate dehydrogenase by PC12 cells. SAL enhanced Akt phosphorylation in PC12 cells, and the protective effects of SAL against MPP⁺-induced apoptosis were abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation. These findings suggest that SAL prevents MPP⁺-induced apoptosis in PC12 cells, at least in part through activation of the PI3K/Akt pathway.     

Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector

We investigated the age-related alterations in nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), parvalbumin and neuronal nitric oxide synthase (nNOS) immunoreactivity of the mouse hippocampal CA1 sector. NGF and BDNF immunoreactivity was unchanged in the hippocampal CA1 pyramidal neurons from 2 to 50-59 weeks of birth. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector from 40-42 to 50-59 weeks of birth. On the other hand, the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. Our results indicate that NGF and BDNF immunoreactivity was unaltered in the hippocampal CA1 pyramidal neurons during aging processes. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector during aging processes. The present study also shows that the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. These results demonstrate that the expression of glial NGF and BDNF may play a key role for helping survival and maintenance of pyramidal neurons and neuronal functions in the hippocampal CA1 sector during aging processes. Furthermore, our findings suggest that parvalbumin- and nNOS-positive interneurons in the hippocampal CA1 sector are resistant to aging processes. Moreover, our findings suggest that nitric oxide synthesized by the nNOS may play some role for neuronal growth during postnatal development.     

鼠神经生长因子对新生儿缺氧缺血性脑病患儿血清神经肽Y和神经元特异性烯醇化酶水平的影响及疗效观察

摘 要 目的： 探讨鼠神经生长因子对新生儿缺氧缺血性脑病(HIE)患儿血清神经肽Y(NPY)和神经元特异性烯醇化酶(NSE)水平的影响及疗效观察。方法: 采用随机数字表法将70例新生儿HIE患儿分成观察组和对照组。两组患儿均予以吸氧、控制颅内压、血压和血糖,抗惊厥、保持水电解质平衡等常规治疗。观察组患儿加用鼠神经生长因子20 μg, im,qd。对照组患儿加用胞磷胆碱注射液100 mg,ivd,qd,均连用10～14 d。观察两组患儿治疗前后血清NPY 和NSE水平变化,比较两组疗效及药品不良反应,随访1年内神经系统后遗症的发生率。结果: 治疗2周后,两组血清NPY和NSE水平较前均明显下降(P<0.05和P<0.01),且观察组下降幅度明显大于对照组(P<0.05);观察组临床总有效率为94.28%,明显高于对照组的68.57%(P<0.01),两组患儿治疗中未出现明显药品不良反应。随访观察1年,观察组后遗症的发生率明显低于对照组(P<0.05)。结论: 鼠神经生长因子治疗新生儿HIE的疗效肯定,安全性好,可促进受损神经元细胞的修复,减少神经系统后遗症的发生率,其作用与降低血清NPY和NSE水平密切相关。     

NGF与细胞凋亡

神经长生因子是一种影响神经细胞发育、存活的多能神经营养因子，其中枢和周围效应与神经细胞凋亡密切相关。本文对NGF与神经系统发育、神经损伤及疾病过程中所发生的细胞凋亡的关系以及NGF的抗凋亡作用等方面的研究状况进行了综述。     

Growth factor signalling in osteoarthritis

Osteoarthritis (OA) is one of the most common diseases, affecting more than 10% of populations and thus creating immense socioeconomic burden. The pathological changes of OA involve the entire joint, which is composed of multiple types of tissues and cells, exemplified by cartilage degradation, subchondral bone thickening, osteophyte formation, synovium inflammation and hypertrophy, and ligament degeneration. As joint homeostasis requires a complex network of growth factors to regulate anabolic and catabolic events, the dysregulation of growth factor signalling would have negative impacts on structure and function of multiple joint tissues and eventually lead to the onset and progression of OA. In this review, we will discuss TGF-β, NGF, Hedgehog and Wnt, the four growth factors which have received extensive attention in the field of OA and clinical/translational interrogation about their application in OA therapies.     

Inhibition by Methylprednisolone Acetate Suggests an Indirect Mechanism for TGF-B Induced Angiogenesis

Abstract

Angiogenesis induced by transforming growth factor beta (TGFB) implanted in the rabbit cornea is accorripanied by an influx of inflammatory cells. To determine if the inflammatory cells are the mediators of the neovascularization, they were depleted by local administration of methylprednisolone acetate (MPA). Subconjunctival injections of 16 mg of MPA immediately following implantation of 50 ng of TGFB in the cornea prevented the inflammation and subsequent formation of capillaries. If the injections of MPA were delayed by 48 hr and the inflammatory cells were allowed to enter the cornea, angiogenesis occured, demonstrating that MPA had no adverse effects on the ability of endothelial cells to form capillaries. These results confirm the hypothesis that TGFB induces angiogenesis indirectly by recruiting inflammatory cells capable of stimulating direct angiogenesis.