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Background Autism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown. Methods Male pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals. Results At PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered. Conclusions Our study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model.

The central nervous system is widely known to exert control over our systemic physiology via several mechanisms including the regulation of skeletal metabolism. Neuronal circuits within the hypothalamus have been shown to impact bone mass via leptin-dependent and independent mechanisms; however, the full extent to which the brain controls bone homeostasis is not known. We previously identified cell adhesion molecule1 (Cadm1) as a regulator of body weight and energy homeostasis via its expression in multiple regions of the brain. Here, we show that loss of Cadm1 expression in excitatory neurons results in increased leptin sensitivity in addition to a concomitant reduction in bone mass. Femoral length, bone mineral content, diaphyseal cross-sectional area, and bone strength were all lower in Cadm1-deficient animals. Conversely, inducing expression of Cadm1 in excitatory neurons decreased leptin sensitivity and increased femoral length, bone mineral content, and diaphyseal cross-sectional area. Together, these results illustrate an essential role for this synaptic protein in the neuronal regulation of skeletal bone metabolism.

It was found that considerable structure-dependent changes in the distribution of neuronal cell adhesion molecules (NCAM) are observed in the brain of rats under conditions of doxorubicin-induced cardiomyopathy. This is accompanied by decreases in the intensity of locomotor and orientational/ research activity of the animals and changes in the stress-related indices in the “Open field” test.

Neuron-glial-related cell adhesion molecule (NRCAM) is a neuronal cell adhesion molecule of the L1 immunoglobulin superfamily, which plays diverse roles during nervous system development including axon growth and guidance, synapse formation, and formation of the myelinated nerve. Perturbations in NRCAM function cause a wide variety of disorders, which can affect wiring and targeting of neurons, or cause psychiatric disorders as well as cancers through abnormal modulation of signaling events. In the present study, we characterize the Xenopus laevis homolog of nrcam. Expression of Xenopus nrcam is most abundant along the dorsal midline throughout the developing brain and in the outer nuclear layer of the retina.

Bioorthogonal chemistry refers to chemical reactions that can occur within a living system without altering native biochemical processes. Applications of this concept extend to studies on a group of biomolecules that includes glycans, proteins, and lipids. In this study, a strategy for isolating cell surface glycoproteins and based on bioorthogonal chemistry was employed to identify new cancer-related glycoproteins. A novel alkyne reagent containing one disulfide bond was synthesized for the enrichment of glycoproteins metabolized with peracetylated N-azidoacetylmannosamine, which was applied on three different cancer cell lines, and all isolated proteins were analyzed by high-performance liquid chromatography-tandem mass spectrometry. The strategy of purifying cell surface glycoproteins introduced in this article was shown to be reliable, and a total of 56 cell surface glycoproteins were identified. Neuronal cell adhesion molecule was found uniquely expressed in A549 lung adenocarcinoma, and its expression in non-small-cell lung carcinomas was detected by immunohistochemistry. Furthermore, a significant increase of neuronal cell adhesion molecule expression was identified in non-small-cell lung adenocarcinoma compared with adjacent noncancerous tissues, and could be a novel potential target and marker in cancer treatment and detection.

We showed that, under conditions of experimental chronic hepatitis, excessive increases in the levels of a Ca-binding protein, S-100b, and a neuronal cell adhesion molecule, NCAM, occur in all parts of the brain of Wistar rats. This is accompanied by suppression of locomotor and orientational/research activity of the animals and increase in their stress sensitivity. Treatment by α ketoglutarate and cytoflavin in chronic hepatitis provides a clear neuroprotective effect.

We demonstrated that, under conditions of the development of experimental pancreatitis accompanied by a decrease in locomotor and orientational-research activity of animals and also by the development of the stress state, concentrations of the soluble and membrane isoforms of neuronal cell adhesion molecule (NCAM) change in the cerebellum and thalamus.

For investigation of histogenesis of central neurocytomas (CNs), subependymoma (SEs), subependymal giant cell astrocytomas (SEGAs), we studied expression of various neuronal and glial biomarkers by immunohistochemical (IHC) study and reverse transcriptase-polymerase chain reaction (RT-PCR). The materials for IHC were paraffin section of seven CNs, three SEs, and eight SEGAs and those for RT-PCR were frozen tissues of seven CNs, three SEs, and five SEGAs. Control group was five ependymomas (EPs) and four pilocytic astrocytomas (PAs). The neuronal biomarkers included nestin, chromogranin A (chrA), synaptophysin (SNP), neuronal cell adhesion molecule (NCAM), neuron specific enolase (NSE), neuronal nuclear antigen (NeuN), neurofilament (NF) and the glial marker was GFAP. CNs expressed all neuronal markers except NF (0%), SNP (100%), NCAM (100%), NSE (100%), NeuN (100%), nestin (29%) and chrA (43%), but GFAP expression was found only in one case (14%). SEGA coexpressed several neuronal markers and a glial marker; NeuN (100%), NSE (88%), NCAM (63%), nestin (100%), SNP (weakly and focally, 100%), and GFAP (100%), however, other neuronal markers including chrA, SNP and NF were all negative. SE expressed nonspecific neuronal markers (NCAM (100%) and NSE (100%)) which showed weak intensity and a GFAP (100%), but not nestin. Among control cases of EPs and PAs, no one case expressed neuronal markers except nonspecific neuronal marker of NCAM, but robustly expressed GFAP. RT-PCR product of nestin was expressed in 29% of CNs (2/7cases), 60% of SEGAs (3/5 cases), 100% of SEs (3/3 cases), 80% of EPs (4/5 cases), and 25% of PAs (1/4 cases). Conclusively, coexpression of neuronal and glial markers and expression of nestin in CNs, SEGAs and SEs suggested the origin of these tumor cells might be the stem cells being able to differentiate into both neuronal and glial phenotypes. But CNs might be originated from rather neuronally committed stem cells and SEs from rather glially committed stem cells.

Stress has profound effects on brain structure and function, but the underlying mechanisms are still poorly understood. Recent studies imply that neuronal cell adhesion molecules of the immunoglobulin superfamily--NCAM and L1--are important mediators of the effects of stress on the brain. Chronic stress regimes that lead to hippocampal atrophy and spatial-learning impairment in rodents simultaneously induce a pattern of changes in cell adhesion molecule expression that fits with a role for these molecules in stress-induced neuronal damage and neuroprotective mechanisms. These findings highlight cell adhesion molecules as potential therapeutic targets to treat stress-related cognitive disturbances.

Under conditions of experimental varicocele in rats, we observed suppression of production of testosterone and significant drops in the level of this hormone in the blood serum. Such a decrease resulted in a two-fold (or even greater) rise in the amount of the membrane-bound fraction of neuronal cell adhesion molecule (NCAM) in the hypothalamus and hippocampus, while the levels in the cerebellum and neocortex remained stable, and also in appreciable redistribution of the soluble form of this molecule in different cerebral structures in the course of development of varicocele.

We studied the dynamics of expression of neuronal cell adhesion molecule (NCAM) in the hippocampus of rats trained to perform conditioned active avoidance reaction (CAAR). Using a hard-phase immunoenzyme analysis technique, we quantitatively measured the NCAM content in the membrane fraction of hippocampal tissue and observed a statistically significant increase in this index on the third day and a certain decrease within the second to fourth weeks of the training course. These results confirm the statement that changes in the level of NCAM expression in the hippocampus of experimental animals can be one of the mechanisms providing plastic synaptic modifications in the processes of learning and formation of memory engrams and are also indicative of the important role of the hippocampus in such a formation.

Cell-cell and cell-matrix interactions are essential for many basic functions, including differentiation and development. In pathological conditions such as inflammation and tumorigenesis adhesive events also play a major role. Cellular adhesion is mediated by specific molecules expressed by both normal and neoplastic tissues. Capillary hemangioblastoma is a tumor of controversial origin, characterized by two major components, vacuolated stromal cells and a capillary network. In order to shed light on the differentiation of the stromal cells and the interactions between the two major components of hemangioblastoma we studied the expression of several adhesion molecules by immunocytochemistry. The endothelium-associated adhesion molecules (ICAM-1, ICAM-2, VCAM-1, PECAM-1 and ELAM-1) were expressed by endothelial cells within the tumors, but not by stromal cells. In contrast, the stromal cells showed strong neuronal cell adhesion molecule (NCAM/CD56) expression, further distinguishing them from endothelial cells. In addition, the stromal cells expressed CD44, which is of interest, as this membrane protein is linked to ezrin, a cytoskeleton-associated protein also expressed by stromal cells. We conclude that the stromal cells and endothelial cells of capillary hemangioblastoma exhibit quite divergent expression patterns of adhesion molecules. The NCAM expression in stromal cells suggests neuroectodermal or mesenchymal differentiation of this tumor. In addition, the NCAM expression could contribute to the sometimes problematic differential diagnosis between capillary hemangioblastoma and metastatic renal cell carcinoma of the central nervous system.

A comparative study of the role of specific adhesion proteins, NCAM (neuronal cell adhesion molecules) and N-cadherin, was carried out on rats subjected to passive avoidance training procedure. It was shown that antibodies against the Ca2+-dependent adhesion protein N-cadherin injected into the rat somatosensory cortical zone 6 h after passive avoidance training had been completed did not evoke a loss of the habit by experimental animals. At the same time, an absolute amnestic effect with respect to this reflex developed after injection of antibodies against NCAM. After injection of antibodies against the above-mentioned proteins into the dorsal part of the hippocampus, the avoidance habit also disappeared in the case of treatment with antibodies against NCAM and was kept under the influence of antibodies against N-cadherin. The data obtained testify that NCAM and N-cadherin play dissimilar roles in the formation of a memory trace in the course of training.

Background The polysialylated neuronal cell adhesion molecule (PSA-NCAM) is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG) and brainstem neuronal populations at prenatal and adult age. Results Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age, the distribution pattern remains fairly steady, whereas the density of immunoreactive structures and the staining intensity may change and are usually higher in newborn than in adult specimens. Conclusion The results obtained show that, in man, the expression of PSA-NCAM in selective populations of central and peripheral neurons occurs not only during prenatal life, but also in adulthood. They support the concept of an involvement of this molecule in the structural and functional neural plasticity throughout life. In particular, the localization of PSA-NCAM in TG primary sensory neurons likely to be involved in the transmission of protopathic stimuli suggests the possible participation of this molecule in the processing of the relevant sensory neurotransmission.

There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind rabies virus and/or facilitate rabies virus entry into cells. Other components of the cell membrane, such as gangliosides, may also participate in the entry of rabies virus. However, little is known of the role of these molecules in vivo. This review proposes a speculative model that accounts for the role of these different molecules in entry and trafficking of rabies virus into the nervous system.

Recruitment of new neurons to existing circuits is a fascinating form of adult plasticity. In the mammalian brain, this process occurs in two discrete regions, the subventricular zone of the lateral ventricule (SVZ) and the subgranular zone of dentate gyrus (SGZ) in the hippocampus. Several recent studies suggest that isoforms of the neuronal cell adhesion molecule (NCAM) carrying the linear homopolymer of alpha 2,8-linked sialic acid (polysialic acid, PSA), play a role in regulating several steps of adult neurogenesis including migration, survival and process outgrowth of newly generated neurons. Here, we will review recent evidence on how PSA-NCAM might regulate the biological properties of new neurons in sites of adult neurogenesis.

The content of NCAM, the neural cell adhesion molecule, was studied in the cerebral cortex, hippocampus, striatum, cerebellum, and pons of 15- and 30-day-old rats, the offspring of intact females and females subjected to stress during pregnancy. At the 30th day of the postmatal development, opposite NCAM concentration changes were observed in the cortex and other brain parts of the offspring of stressed rats. These differences can be related to a deficiency of mature synapses in the forebrain of prenatally stressed rats and adaptation rearrangements in the neuronal systems of the brainstem and cerebellum.