NCAM

There is increasing evidence for adolescence as a time period vulnerable to environmental perturbations such as stress. What is unclear is the persistent nature of the effects of stress and how specific these effects are to the type of stressor. In this review, we describe the effects of chronic, unpredictable stress (CUS) exposure during adolescence on adult behavior and brain morphology and function in animal models. We provide evidence for adolescence as a critical window for the effects of physical CUS that persist into adulthood, with ramifications for morphological development, associated hippocampal-dependent tasks, and anxiety- and depressive-like behaviors. The results of this investigation are contrasted against those of social CUS stress exposure from the same time period that show reversible and, in the case of responses to drugs of abuse, potentially protective effects in adulthood. Finally, we discuss potential underlying mechanisms for these morphological and behavioral findings. It is our aim that the research highlighted in this review will aid in our understanding of the role of stress in adolescent mental health and development. This article is part of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid System.

This paper examines the role of Research Libraries as regard the information needs of Agric Engineers
in Nigeria, using the National Centre for Agricultural Mechanization library as a case study. It further
stressed the importance of the library in Agricultural Engineering Research cum its effect on research
development. Recommendations on how to further improve the impact of the library on Agric.
Engineering Research were also highlighted

The activation of synaptic N-methyl-D-aspartate-receptors (NMDARs) is crucial for induction of synaptic plasticity and supports cell survival, whereas activation of extrasynaptic NMDARs inhibits long-term potentiation and triggers neurodegeneration. A soluble polysialylated form of the neural cell adhesion molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B-containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism result in impaired synaptic plasticity and learning, which could be repaired by reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or downstream signaling through RasGRF1 and p38 MAP kinase. Ectodomain shedding of NCAM, and hence generation of soluble NCAM, is controlled by metalloproteases of a disintegrin and metalloprotease (ADAM) family. As polySia-NCAM is predominantly associated with GABAergic interneurons in the prefrontal cortex, it is noteworthy that EphrinA5/EphA3-induced ADAM10 activity promotes polySia-NCAM shedding in these neurons. Thus, in addition to the well-known regulation of synaptic NMDARs by the secreted molecule Reelin, shed polySia-NCAM may restrain activation of extrasynaptic NMDARs. These data support a concept that GABAergic interneuron-derived extracellular proteins control the balance in synaptic/extrasynaptic NMDAR-mediated signaling in principal cells. Strikingly, dysregulation of Reelin or polySia expression is linked to schizophrenia. Thus, targeting of the GABAergic interneuron-principle cell communication and restoring the balance in synaptic/extrasynaptic NMDARs represent promising strategies for treatment of psychiatric diseases.

In this study we surveyed a total of 218 cerebrospinal fluid (CSF) samples from patients with different neurological diseases including Alzheimer disease, non-Alzheimer forms of dementia, other neurodegenerative diseases without dementia and normal controls to quantitate by capture ELISA the concentrations of the immunoglobulin superfamily adhesion molecules L1 and NCAM, and characterized by immunoblot analysis the molecular forms of L1 and NCAM. We found a significant increase of L1 and a strong tendency for increase of the soluble fragments of NCAM in the CSF of Alzheimer patients compared to the normal control group. The proteolytic fragments of L1, but not NCAM were also elevated in patients with vascular dementia and dementia of mixed type. Higher L1 concentrations were observed irrespective of age and gender. NCAM concentrations were independent of gender, but positively correlated with age and, surprisingly, also with incidence of multiple sclerosis. Thus, there was an influence of Alzheimer and non-Alzheimer dementias and neurodegeneration on L1, whereas age and neurodegeneration influenced NCAM concentrations. These observations point to an abnormal processing and/or shedding of L1 and NCAM in dementia-related neurodegeneration and age, respectively, reflecting changes in adhesion molecule-related cell interactions.

Adhesive interactions are important for cell trafficking, differentiation, function and tissue differentiation. Neural cell adhesion molecule (NCAM) is involved in a diverse range of contact-mediated interactions among neurons, astrocytes, oligodendrocytes, and myotubes. It is widely but transiently expressed in many tissues early in embryogenesis. Four main isoforms exist but there are many other variants resulting from alternative splicing and post-translational modifications. This review discusses the actions and association of N-CAM and variants, PSA CAM. L1CAM and receptor tyrosine kinase. Their interactions with the interstitial cells of Cajal - the pacemaker cells of the gut in the manifestation of gut motility disorders, expression in carcinomas and mesenchymal tumours are discussed.

The neural cell adhesion molecule (NCAM) mediates cell-cell and cell-matrix adhesion. It is broadly expressed in the nervous system and regulates neurite outgrowth, synaptogenesis, and synaptic plasticity. Previous in vitro studies revealed that palmi-toylation of NCAM is required for fibroblast growth factor 2 (FGF2)-stimulated neurite outgrowth and identified the zinc finger DHHC (Asp-His-His-Cys)-containing proteins ZDHHC3 and ZDHHC7 as specific NCAM-palmitoylating enzymes. Here, we verified that FGF2 controlled NCAM palmitoylation in vivo and investigated molecular mechanisms regulating NCAM palmi-toylation by ZDHHC3. Experiments with overexpression and pharmacological inhibition of FGF receptor (FGFR) and Src revealed that these kinases control tyrosine phosphorylation of ZDHHC3 and that ZDHHC3 is phosphorylated by endogenously expressed FGFR and Src proteins. By site-directed mutagenesis, we found that Tyr18 is an FGFR1-specific ZDHHC3 phosphory-lation site, while Tyr295 and Tyr297 are specifically phosphorylated by Src kinase in cell-based and cell-free assays. Abrogation of tyrosine phosphorylation increased ZDHHC3 autopalmitoylation, enhanced interaction with NCAM, and upregulated NCAM palmitoylation. Expression of ZDHHC3 with tyrosine mutated in cultured hippocampal neurons promoted neurite outgrowth. Our findings for the first time highlight that FGFR-and Src-mediated tyrosine phosphorylation of ZDHHC3 modulates ZD-HHC3 enzymatic activity and plays a role in neuronal morphogenesis.

The present results show that the expression of Growth Arrest Specific1 (Gas1) in SH-SY5Y neuroblastoma cells significantly inhibits the increased phosphorylation of tyrosine 1062 of the Ret receptor tyrosine kinase induced by glial-cell-line-derived neurotrophic factor (GDNF). We also observed that Gas1 significantly reduces the activation of Akt. GDNF and members of its family of ligands (GFLs), signal through a molecular complex consisting of one of its receptors (GFRαs) and the Ret receptor tyrosine kinase. GDNF is a key component to preserve several cell populations in the nervous system, including dopaminergic and motor neurons, and also participates in the survival and differentiation of peripheral neurons such as enteric, sympathetic and parasympathetic. On the other hand, Gas1 is a molecule involved in cell arrest that can induce apoptosis when over-expressed in different cell lines, including cells of neuronal and glial origin. Although, Gas1 is widely expressed during development, its role in vivo has not yet been clearly defined. We recently showed the structural homology between Gas1 and GFRαs, thus suggesting that the physiological role of Gas1 is that of modulating the biological responses induced by GDNF and/or other members of this family of signaling molecules. The results of this work are consistent with the hypothesis of Gas1 acting as a negative modulator of GDNF signaling.

Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1beta (IL-1beta) and the impairment in long-term potentiation (LTP). We report that the age-related increase in microglial activation was accompanied by decreased expression of neuronal CD200, and suggest that the proclivity of FGL to suppress microglial activation is due to its stimulatory effect on neuronal CD200. We demonstrate that FGL enhanced interleukin-4 (IL-4) release from glial cells and IL-4 in turn enhanced neuronal CD200 in vitro. We provide evidence that the increase in CD200 is reliant on IL-4-induce...

Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1β

Cytokeratins 7 and 19 and neuronal cell adhesion molecule (CD56) are differentially expressed in the hepatocytes and biliary epithelium. CD34 is an endothelial marker that is expressed in hepatic sinusoids in conditions associated with altered vascular flow and neoplasms. Distinct staining patterns using these markers have been shown in resected specimens of focal nodular hyperplasia, telangiectatic focal nodular hyperplasia, and hepatic adenoma. The purpose of this study was to examine the diagnostic use of these markers in needle biopsies. Needle biopsies from focal nodular hyperplasia (n = 21), telangiectatic focal nodular hyperplasia (n = 2), and hepatic adenoma (n = 14) were included in the study. These cases represent typical examples of each entity that have been diagnosed on the basis of clinical, imaging, and histologic features. Corresponding resection specimens available in 9 cases were also included in the study for comparison. Immunohistochemical analysis was performed ...

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed...

AlphaII-spectrin, a basic component of the spectrin-based scaffold which organizes and stabilizes membrane microdomains in most animal cells, has been recently implicated in cell adherence and actin dynamics. Here we investigated the contribution of αΙΙ-spectrin to neuritogenesis, a highly complex cellular process which requires continuous actin cytoskeleton remodeling and cross-talk between extracellular cues and their cell surface receptors, including cell adhesion molecules. Using RNA interference-mediated gene silencing to down-regulate αΙΙ-spectrin expression in human neuroblastoma SH-SY5Y cells, we observed major changes in neurite morphology and cell shape: (1) reduced mean length and a higher number of neurites per cell; occasional long neurites were thinner and displayed abnormal adhesiveness during cell migration resulting in frequent breaks; similar persisting adhesiveness and breaks were also observed in trailing edges of cell bodies; (2) irregular polygonal cell shape in parallel with loss of cortical F-actin from neuronal cell bodies; (3) reduction in protein levels of αΙ- and βΙ-spectrins, but not βΙΙ-spectrin (4) decreased global expression of adhesion molecule L1 and spectrin-binding adapter ankyrin-B, which links L1 to the plasma membrane. Remarkably, αΙΙ-spectrin depletion affected L1 - but not NCAM - cell surface expression, and L1 clustering at growth cones. This study demonstrates that αΙΙ-spectrin is implicated in normal morphology and adhesive properties of neuron cell bodies and neurites, and in cell surface expression and organization of adhesion molecule L1.

The controlled differentiation of embryonic stem (ES) cells is of utmost interest to their clinical, biotechnological, and basic science use. Many investigators have combinatorially assessed the role of specific soluble factors and extracellular matrices in guiding ES cell fate, yet the interaction between neighboring cells in these heterogeneous cultures has been poorly defined due to a lack of conventional tools to specifically uncouple these variables. Herein, we explored the role of cell–cell interactions during neuroectodermal specification of ES cells using a microfabricated cell pair array. We tracked differentiation events in situ, using an ES cell line expressing green fluorescent protein (GFP) under the regulation of the Sox1 gene promoter, an early marker of neuroectodermal germ cell commitment in the adult forebrain. We observed that a previously specified Sox1-GFP+ cell could induce the specification of an undifferentiated ES cell. This induction was modulated by the two cells being in contact and was dependent on the age of previously specified cell prior to coculture. A screen of candidate cell adhesion molecules revealed that the expression of connexin (Cx)-43 correlated with the age-dependent effect of cell contact in cell pair experiments. ES cells deficient in Cx-43 showed aberrant neuroectodermal specification and lineage commitment, highlighting the importance of gap junctional signaling in the development of this germ layer. Moreover, this study demonstrates the integration of microscale culture techniques to explore the biology of ES cells and gain insight into relevant developmental processes otherwise undefined due to bulk culture methods.