Age-dependent modifications in vascular adhesion molecules and apoptosis after 48-h reperfusion in a rat global cerebral ischemia model

Stroke is one of the leading causes of death and permanent disability in the elderly. However, most of the experimental studies on stroke are based on young animals, and we hypothesised that age can substantially affect the stroke response. The two-vessel occlusion model of global ischemia by occluding the common carotid arteries for 15 min at 40 mmHg of blood pressure was carried out in 3- and 18-month-old male Sprague–Dawley rats. The adhesion molecules E- and P-selectin, cell adhesion molecules (CAMs), both intercellular (ICAM-1) and vascular (VCAM-1), as well as glial fibrillary acidic protein (GFAP), and cleaved caspase-3 were measured at 48 h after ischemia in the cerebral cortex and hippocampus using Western blot, qPCR and immunofluorescence techniques. Diametric expression of GFAP and a different morphological pattern of caspase-3 labelling, although no changes in the cell number, were observed in the neurons of young and old animals. Expression of E-selectin and CAMs was also modified in an age- and ischemia/reperfusion-dependent manner. The hippocampus and cerebral cortex had similar response patterns for most of the markers studied. Our data suggest that old and young animals present different time-courses of neuroinflammation and apoptosis after ischemic damage. On the other hand, these results suggest that neuroinflammation is dependent on age rather than on the different vulnerability described for the hippocampus and cerebral cortex. These differences should be taken into account in searching for therapeutic targets.     

Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma

The immunocytochemical expression of cadherins and catenins was examined during the process of oral carcinogenesis by comparing their expression in normal and dysplastic epithelium with primary and metastatic carcinomas. While control epithelium showed normal distribution for P and E cadherin and the catenins, in severe dysplasia P-cadherin was upregulated. In other cases and in carcinoma- in-situ adjacent to infiltrating carcinomas, membranous expression of the cadherins and catenins was reduced or lost. The changes in expression of E-cadherin and the catenins suggest that disruption of the E-cadherin/catenin complex is a late event associated with invasion. In primary carcinomas reduced membranous and cytoplasmic staining were observed for both cadherins and catenins. Abnormal localisation of E-cadherin occurred in the more superficial parts of the better differentiated carcinomas, suggesting abnormality to the E-cadherin complex(es). In contrast, membranous expression of cadherins and catenins was reduced or lost in the deep invasive margin of primary carcinomas and in most poorly differentiated carcinomas. For E-cadherin at least, this reduction appears associated with differentiation, invasion and possibly prognosis. Possible mechanisms involved for changes in expression of the cadherins and associated catenins and areas for further study are discussed.     

Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic β1-integrin

β1-containing integrins are required for persistent synaptic potentiation in hippocampus and regulate hippocampal-dependent learning. Based largely on indirect evidence, there is a prevailing assumption that β1-integrins are localized at synapses, where they contribute to synapse adhesion and signaling, but this has not been examined directly. Here we investigate the fine localization of β1-integrin in adult mouse hippocampus using high-resolution immunogold labeling, with a particular emphasis on synaptic labeling patterns. We find that β1-integrins localize to synapses in CA1 and are concentrated postsynaptically. At the postsynaptic membrane, β1-integrins are found more commonly clustered near active zone centers rather than at the peripheral edges. In mice harboring a conditional deletion of β1-integrins, labeling for N-cadherin and neuroligins increases. Western blots show increased levels of N-cadherin in total lysates and neuroligins increase selectively in synaptosomes. These data suggest there is a dynamic, compensatory adjustment of synaptic adhesion. Such adjustment is specific only for certain cell adhesion molecules (CAMs), because labeling for SynCAM is unchanged. Together, our findings demonstrate unequivocally that β1-integrin is an integral synaptic adhesion protein, and suggest that adhesive function at the synapse reflects a cooperative and dynamic network of multiple CAM families.     

Soluble cell adhesion molecules in monocytes of Alzheimer’s disease and mild cognitive impairment

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with characteristic neuropathological features that are accompanied by inflammatory processes and release of pro-inflammatory cytokines. There is evidence that microglial cells are a key mediator of damage in AD. The microglial compartment may arise to a greater part from activation and transmigration of circulating monocytes. The aim of the present pilot study was to explore, if different cell adhesion molecules (ICAM-1 and -3, PECAM-1, VCAM-1, P-, L- and E-selectins, E-cadherin), RAGE and CD14 are affected in monocytes of healthy subjects compared to patients suffering from AD or mild cognitive impairment (MCI). Monocytes were isolated by negative magnetic selection (MACS) from EDTA blood samples, and extracts were analyzed by Searchlight Multiplex ELISAs. When compared to healthy subjects, the ratio of monocytic ICAM-3/CD14 was significantly decreased in MCI and AD patients and the ratio of the monocytic P-selectin/CD14 was specifically decreased in AD patients. In conclusion, our data show that monocytic cell adhesion molecules are decreased in AD and MCI patients. Further larger longitudinal studies should then clarify whether any of these parameters may be useful as a diagnostic biomarker.     

Plasticity of neurohypophysial terminals with increased hormonal release during dehydration: ultrastructural and biochemical analyses

Arginine vasopressin- (AVP) and oxytocin- (OXT) secreting magnocellular neurons undergo gross structural changes with chronic physiological stimulation. Here, we investigated subcellular aspects of plasticity in rat neurohypophysial terminals during dehydration. Ultrastructural analyses demonstrated that chronic dehydration by 2% NaCl drinking for 7 days significantly decreased the numbers of neurosecretory granules and microvesicles but not the numbers of mitochondria. Moreover, in dehydrated rats, terminals making neurovascular contacts enlarged, whereas terminals in apposition to astrocytes, i.e., neuroglial contacts, became smaller. Western blot analyses demonstrated significant decreases in the levels of F3 and Thy-1 together with those of AVP- and OXT-neurophysin, but the levels of synaptophysin, SNAP-25, and GAP-43 were unchanged. Both F3 and Thy-1 were recovered in the buffer-insoluble pellet, and phosphatidyl inositol-specific phospholipase C treatment released both molecules from the crude membrane fraction, indicating that they are attached to terminal membranes by glycosylphosphatidyl inositol anchors. Confocal microscopic observations demonstrated that F3 colocalized with Thy-1 in the same terminals of magnocellular neurons. In contrast, the level of calretinin, a Ca(2+) binding protein was significantly increased with chronic dehydration. Thus, the present results suggest that enhancement of neurovascular contacts results from rearrangement of terminal-astrocyte and terminal-vessel contacts rather than enlargement or sprouting of magnocellular terminals themselves. The down-regulation of F3 and Thy-1 may contribute to enhancement of neurovascular contacts that accompany increased peptide release during dehydration.     

sICAM-1是尿白蛋白正常2型糖尿病病人血管病变的早期监测指标

为探讨有或无微量白蛋白尿的 2型糖尿病患者血浆sICAM 1 (可溶性细胞间黏附分子 )、sVCAM 1 (可溶性血管细胞黏附分子 )水平的变化 ,并以血浆vWF水平作为内皮功能损伤的指标 ,观察血浆黏附分子水平与vWF水平之间的关系 ,应用ELISA法检测了 82例 2型糖尿病患者 (其中 5 7例尿白蛋白正常、2 5例伴微量白蛋白尿 )的血浆sICAM 1、sVCAM 1、vWF水平 ,并与 2 8例健康人作对照。再将结果与空腹血糖、糖化血红蛋白、尿微量白蛋白、三酰甘油、总胆固醇、高密度脂蛋白、低密度脂蛋白、空腹胰岛素水平进行相关分析。结果 :在尿白蛋白正常且血浆vWF水平正常的 2型糖尿病患者中 ,血浆sICAM 1水平已有显著升高 (P <0 .0 5 ) ,且与BMI、三酰甘油密切相关。提示 :血浆sICAM 1可替代vWF作为 2型糖尿病患者早期血管病变预测和监测的指标     

Role of upregulated miR-136-5p in lung adenocarcinoma: A study of 1242 samples utilizing bioinformatics analysis

Background

It is generally acknowledged that miRNAs play pivotal roles in the initiation and development of cancer. The aim of the current study is to investigate the clinicopathological role of miR-136-5p in lung adenocarcinoma and its underlying molecular mechanism.