Zileuton ameliorates depressive-like behaviors,hippocampal neuroinflammation,apoptosis and synapse dysfunction in mice exposed to chronic mild stress

Our previous study has found that zileuton, a selective 5-lipoxygenase (5LO) inhibitor, abrogated lipopolysaccharide-induced depressive-like behaviors and hippocampal neuroinflammation. Herein, we further extended our curiosity to investigate effects of zileuton on stress-induced depressive-like behaviors. Our data indicated that zileuton significantly ameliorated depressive-like behaviors in mice subjected to chronic mild stress (CMS), as shown in the tail suspension test, forced swimming test and novelty-suppressed feeding test. The further studies indicated that zileuton suppressed hippocampal neuroinflammation, evidenced by lower levels of TNF-α, IL-1β and nuclear NF-κB p65 as well as decreased number of Iba1-positive cells. It also significantly ameliorated hippocampal apoptosis, indicated by deceased number of TUNEL-positive cells, deceased ratio of cleaved caspase-3/procaspase-3 and increased ratio of Bcl-2/Bax. More importantly, zileuton increased the level of synaptic proteins PSD-95 and SYN and the number of NeuN⁺/BrdU⁺ cells in the hippocampus. Over all, zileuton alleviated CMS-induced depressive-like behaviors, neuroinflammatory and apoptotic responses, abnormalities of synapse and neurogenesis in the hippocampus, suggesting that it might has beneficial effects on depression.     

Symptomatic Intraspinal Oncocytic Adrenocortical Adenoma

Most intraspinal neoplasms of epithelial origin are metastases from primary carcinomas. Benign epithelial tumors are rarely found at this site. We here present the case of a 44-year-old woman with a lesion in the cauda equina that fulfilled the radiologic criteria of schwannoma and caused clinical symptoms for 3 years. The excised tumor was composed of nests of large polygonal cells with eosinophilic partial granular cytoplasm. Significant atypia, necrosis, and mitosis were absent from this lesion. The tumor showed diffuse positivity for melan-A, synaptophysin, and alpha-inhibin. Steroidogenic factor 1 and cytokeratins 8 and 18 were focally seen in the absence of S-100 and chromogranin. This immunoprofile indicated adrenocortical origin. Ultrastructural examination showed abundant mitochondria, suggesting an oncocytic tumor. The diagnosis of an oncocytic adrenal cortical adenoma was made. These extraadrenal tumors are thought to arise from heterotopic adrenocortical tissue in the spinal cavity. Oncocytic tumors are rare neoplasms and they comprise non-functioning variants of adrenal cortical adenomas. To date, only five such intraspinal tumors have been observed. Immunohistochemistry excluded oncocytic paraganglioma, oncocytic meningioma, renal cell carcinoma, alveolar soft part sarcoma, and granular cell tumor. A view of the literature of these rare but probably underdiagnosed intraspinal tumors is given.     

胸髓半横断引起腰髓前角钙网蛋白阳性中间神经元突触联系的变化

为检测大鼠胸髓半横断后后肢运动功能状况和腰髓前角中间神经元的突触联系的变化,并分析其相关关系,本实验通过BBB评分、钙网蛋白(CR)和突触囊泡素(SYN)免疫荧光双标记及相关分析方法进行了研究。结果显示:大鼠胸髓半横断后12 h时,后肢运动功能完全丧失,BBB分值下降,从第3 d开始后肢功能逐渐恢复,BBB分值逐渐增加,至第21 d基本恢复正常;同时观察到腰髓损伤侧12 h时CR免疫反应阳性(CR-IR)神经元周围的SYN-IR降低,第3 d时恢复至正常水平,至第21 d时升高;相关分析显示后肢运动功能BBB评分与CR-IR中间神经元周围的SYN表达水平呈正相关(r=0.45,P<0.05)。上述结果提示大鼠胸髓半横断后,与腰髓CR-IR中间神经元形成的突触联系出现可塑性改变,这种可塑性变化可能是后肢运动功能自发性恢复的形态学基础。     

脑室注射链脲佐菌素对大鼠空间学习记忆能力及海马CA1区神经元数量和海马突触素表达的影响

为了观察脑室内注射链脲佐菌素(streptozotocin,STZ)对大鼠空间学习记忆能力的影响,分析其可能的内在机制,本实验选用40只SD大鼠随机分成对照组和模型组,模型组于第1 d和第3 d脑室注射STZ(总量3 mg/kg)建立Alzheimer病(AD)模型,15 d后进行Morris水迷宫试验,利用RT-PCR方法检测突触素(synaptophysin,SYP)mRNA的表达变化;Nissl染色观察海马结构的改变。结果显示:与对照组相比,脑室注射STZ后大鼠平均上台潜伏期明显延长,穿越平台次数明显减少,靶象限游泳时间的百分比降低,SYP mRNA的表达明显减少,Nissl染色见海马CA1区神经元减少。以上结果提示脑室注射STZ可损伤大鼠的空间学习记忆能力,这可能与海马CA1区神经元和突触结构的损伤有关。     

Immunohistochemical profile and chromosomal imbalances in papillary tumours of the pineal region

The histopathology of papillary tumours of the pineal region (PTPR) closely resembles that of ependymomas and choroid plexus tumours. Therefore, immunohistochemical staining profiles were investigated in a series of 15 PTPR. In addition to cytokeratin, synaptophysin and glial fibrillary acidic protein expression, PTPR were examined for the presence of dot- or ring-like epithelial membrane antigen (EMA) immunoreactivity typically encountered in ependymoma, staining for inwardly rectifying potassium channel Kir7.1 and stanniocalcin-1 (specifically expressed in choroid plexus tumours) as well as microtubule-associated protein-2 (MAP-2). Furthermore, comparative genomic hybridization was performed in five PTPR. Cytokeratin was expressed in all PTPR examined, whereas glial fibrillary acidic protein and synaptophysin staining were absent. Dot- or ring-like EMA immunoreactivity was only observed in 1 out of 15 PTPR. Membranous Kir7.1 and cytoplasmic stanniocalcin-1 staining were present in the minority of PTPR (3/15 and 4/15, respectively). In contrast, MAP-2 immunoreactivity was encountered in 13 out of 15 PTPR, but was significantly less frequently observed in a series of choroid plexus tumours (7/37). PTPR mainly presented with chromosomal losses affecting chromosomes 10 (4/5 cases) and 22q (3/5 cases) as well as gains on chromosomes 4 (4/5 cases), 8 (3/5 cases), 9 (3/5 cases) and 12 (3/5 cases). To conclude, the majority of PTPR can be distinguished from ependymomas and choroid plexus tumours by absent staining for epithelial membrane antigen, Kir7.1 and staniocalcin-1 as well as the presence of distinct MAP-2 immunoreactivity. Antibodies directed against these antigens are thus expected to be valuable markers in the diagnosis of papillary tumours located in the vicinity of the third ventricle.     

Inhibition of hippocampal estrogen synthesis causes region-specific downregulation of synaptic protein expression in hippocampal neurons

Previous studies have shown that synapses and expression of synaptic proteins in hippocampal neurons are regulated by hippocampus-derived estradiol. Here, we compared the effects of this paracrine regulation in different hippocampal regions. In tissue sections, immunohistochemistry followed by semiquantitative image analysis revealed a three-fold higher expression of steroidogenic acute regulatory protein (StAR) and aromatase in neurons of the CA3 than that of the CA1 region and in granule cells. Next, we treated hippocampal cell cultures with letrozole, an aromatase inhibitor, which resulted in a dose-dependent decrease in the release of 17beta-estradiol into the medium and in a dose-dependent downregulation of spinophilin and synaptophysin expression in dissociated hippocampal neurons. The downregulation of synaptic protein expression was restored by simultaneous application of letrozole together with estradiol. In response to a defined dose of letrozole, the downregulation of spinophilin expression was significantly stronger in CA1 neurons and in granule cells, than in cells of the CA3 region in slice cultures. With synaptophysin, downregulation was stronger in stratum lucidum of CA3 than in stratum radiatum of CA1. Both region-specific expression of steroidogenic enzymes and region-specific downregulation of synaptic proteins in response to a defined dose of letrozole may suggest different levels of estrogen concentrations within the hippocampus. Varying concentrations of estradiol in the hippocampus in turn may contribute to region-specific differentiation of hippocampal neurons.     

Expression of erythropoietin and neuroendocrine markers in clear cell renal cell carcinoma

The aim of the study was to investigate the expression of erythropoietin and neuroendocrine markers in clear cell renal cell carcinoma (CCRCC). We retrospectively reviewed the medical records and re‐evaluated histopathological specimens of 33 patients with CCRCC and compared with those of 11 cases of non‐CCRCC. All patients were treated with a partial or radical nephrectomy at St. Olavs Hospital, Trondheim University Hospital, between 2010 and 2016. Thirty‐three patients who were diagnosed with CCRCC had a total of 35 tumours, where 34 of the tumours were CCRCC and one was papillary adenoma. Thirty‐three (97%) of 34 CCRCCs were positive for erythropoietin, and the same 33 (97%) tumours demonstrated strong expression for neuron‐specific enolase (NSE). Two (6%) of 34 CCRCCs had a positive reaction for synaptophysin, and three (9%) of 34 were positive for CD56. Erythropoietin and NSE were negative in non‐CCRCCs, and chromogranin A was negative in all tumours. The above findings suggest that there is a strong association between CCRCC and the expression of erythropoietin and NSE.     

Hippocampal expression of synaptic structural proteins and phosphorylated cAMP response element-binding protein in a rat model of vascular dementia induced by chronic cerebral hypoperfusion

The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group.In addition,the number of accurate crossings over the original platform significantly decreased,hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased,cAMP response element-binding protein expression remained unchanged,and phosphorylated cAMP response element-binding protein expression significantly decreased.Results suggested that abnormal expression of hippocampal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.     

β-淀粉样蛋白与载脂蛋白E4对大鼠海马突触素的影响

目的观察β-淀粉样蛋白（Ap）和载脂蛋白E（apoE）4对大鼠海马突触素（synaptophysin,SYN）的影响以及二者是否具有协同作用。方法将24只雄性Wistar大鼠分为4组：对照组海马注射生理盐水,n13组注射Aβ1-40,apoFA组注射apoE4,Aβ＋apoFA组注射Aβ1-40＋apoFA。15d后水迷宫检测各组大鼠的学习记忆能力,之后免疫组化法检测CA1区突触素的表达。结果apoE4组、Ap组与对照组比较大鼠第5天的逃避潜伏期明显延长,跨台次数明显减少（P〈0．01）;AB组与apoE4组比较,大鼠第5天的逃避潜伏期明显延长,跨台次数明显减少（P〈0．01）;AB与apoFA之间存在交互作用（F=7．098,P〈0．01）。apoE4组、A13组比对照组突触素OD值下降明显（P〈0．01）;Ap组比apoFA组下降明显（P〈0．05）;Aβ＋apoE4组比对照组、apoFA组及Ap组均下降明显（P〈0．01）;Aβ与apoFA具有交互作用（P〈0．05）。结论Aβ及apoE4均可损伤海马突触结构;A13对海马突触结构损伤比apoE4严重。Aβ与apoFA对海马突触结构的损伤具有协同作用。