纳米粒子载体胶质细胞源性神经营养因子在胶质瘤细胞中的表达与作用实验研究

目的观察壳聚糖纳米粒子载体载基因在胶质瘤细胞中表达及其对神经细胞的保护作用。方法采用免疫细胞化学检测胶质细胞源性神经营养因子（GDNF）在胶质细胞瘤细胞中的表达，采用细胞增殖实验（MTT法）观察GDNF对神经细胞的营养作用。结果GDNF在胶质细胞瘤细胞中有表达，在应用纳米粒子载体载基因进入细胞内后GDNF得到高效表达，并保护神经细胞，促进细胞增殖。结论应用纳米粒子载体载基因进入细胞内后可有效提高GDNF表达．并保护神绎细胞．促进细胞增殖。对脊髓损伤后应用这一方法治疗提供理论依据。     

Beneficial actions of neurotrophin treatment on diabetes-induced hypoalgesia in mice

Studies were carried out in streptozotocin-treated diabetic mice to evaluate their behavioral responses to different noxious stimuli. In opposition to rats, streptozotocin-injected diabetic mice display a persistent hypoalgesia to non-noxious mechanical stimulation (von Frey monofilament). Similarly, nocifensive responses of diabetic mice to formalin injection were significantly reduced in both acute and inflammatory phases. However, no overt differences were detected between nondiabetic and diabetic mice in their sensitivity to noxious heat (radiant heat), cold (acetone), or noxious mechanical (pinprick) stimuli applied to the hind paw. To evaluate whether neurotrophin treatment could normalize the sensory deficits, nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was administered intrathecally to diabetic mice for 3 weeks. Neurotrophin-treated mice were also compared to mice that received insulin for 3 weeks. Both NGF and insulin treatment significantly restored mechanical and chemogenic behavioral responses of diabetic mice. In contrast, GDNF treatment only reversed behavioral responses to chemogenic stimuli during the acute phase of the formalin test. These results demonstrate that diabetic mice develop reduced sensitivity to mechanical and chemical stimuli. Furthermore, these studies show that dorsal root ganglion neurons in diabetic mice are responsive to treatment with either NGF or GDNF; however, these 2 neurotrophins differ in their ability to affect distinct somatosensations.     

在小鼠帕金森病模型中观察丙戊酸钠对多巴胺神经元及GDNF表达的影响

目的:通过建立小鼠帕金森病模型,观察丙戊酸钠(valproate,VPA)对中脑黑质多巴胺神经元及胶质源性神经营养因子(glial-derived neurotrophic factor,GDNF)表达的影响,以期探索丙戊酸钠的神经保护作用机制.方法:采用免疫组织化学方法检测小鼠中脑黑质多巴胺神经元;原位杂交方法检测纹...     

GDNF促进帕金森病大鼠模型脑内移植的中脑源神经干细胞表达Pitx3、Nurr1和TH

目的:探讨胶质细胞源性神经营养因子(GDNF)作用下,中脑源神经干细胞(mNSCs)在帕金森病(PD)大鼠模型纹状体移植区表达垂体同源盒家族因子3(Pitx3)、孤儿核受体相关因子1(Nurr1)和酪氨酸羟化酶(TH)的变化.方法:mNSCs单独移植组、mNSCs+GDNF移植组和生理盐水假手术组的PD大鼠模型,移植4...     

Control of Aβ release from human neurons by differentiation status and RET signaling

Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer's disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid β (Aβ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased Aβ secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered Aβ release was associated with rapid upregulation of the GDNF coreceptor “rearranged during transfection” (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased Aβ, whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and Aβ increase. This suggests that RET signaling affects Aβ release from aging neurons.     

神经营养因子与抑郁症

神经营养因子能够调节神经元的生长,并维护神经元可塑性,神经营养因子的缺乏能够导致神经细胞的易损性增加甚至凋亡,本文就目前关于神经营养因子‐3和胶质细胞源性神经营养因子在抑郁症发病过程中的作用进行了讨论,以期为抑郁症的基础研究和临床诊断及治疗提供思路。     

ShcC proteins: Brain aging and beyond

To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.     

The clinical significance of pathological studies of congenital intestinal atresia

Objective

The purpose of this study was to explore the mechanisms of postoperative intestinal motility disorders in intestinal atresia patients by investigating the expression profiles of proteins, including calretinin (CR), glial-derived neurotrophic factor (GDNF), bone morphogenetic protein 2 (BMP-2), c-kit, α-smooth muscle actin (α-SMA), and S-100 protein; to decipher the correlation between the area of the pathological segment and the alteration of the above 6 proteins; and thereby to provide a clinical specific reference values to determine the removal length for intestinal tract resection.

Methods

Immunohistochemistry technique was applied to detect the CR, c-kit, GDNF, BMP-2, α-SMA, and S-100 protein in specimens of atretic, proximal, and distal intestine from 25 cases of intestinal atresia and samples of intestinal walls from 10 non-atresia control specimens. The alteration of the enteric nervous system, nerve growth and its regulatory factors, the interstitial cells of Cajal (ICCs), and the enteric muscle system were examined, with particular attention being paid to pathological changes and the lesion area.

Results

The expression of all of the abovementioned 6 proteins in the proximal side of the atresia was significantly lower than in control group. The expression of the abovementioned proteins tended to be higher farther away from the atresia site. The expressions of both GDNF and BMP-2 had returned to normal level at 10 cm proximal to the atresia site, whereas the expressions of CR, c-kit, α-SMA, and S-100 protein only returned to normal at 15 cm proximal to the atresia site. On the distal side, the expression of all 6 markers at 3 cm distal to the atresia site was normal.

Conclusion

Pathological deterioration of the myenteric ganglia, nerve growth factor, and ICCs are the causes of intestinal motility disorders after the surgical repair of intestinal atresia. Our data support resecting an intestinal segment extending from 15 cm proximal to 3 cm distal to the atretic segment. In proximal jejunal atresia, when it is not possible to resect 15 cm, we suggest resecting as much of the hypertrophic proximal intestine as possible. Based on our data, we believe this surgical practice could improve postoperative dysmotility in these patients.