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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The subventricular zone (SVZ) of the lateral ventricle remains mitotically active in the adult mammalian central nervous system (CNS). Recent studies have suggested that this region may contain neuronal precursors (neural stem cells) in adult rodents. A variety of neuronal and glial markers as well as three extracellular matrix (ECM) markers were examined with the hope of understanding factors that may affect the growth and migration of neurons from this region throughout development and in the adult. This study has characterized the subventricular zone of late embryonic, postnatal, and adult mice using several neuronal markers [TuJ1, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), neuron-specific enolase (NSE)], glial markers [RC-2, vimentin, glial fibrillary acidic protein (GFAP), galactocerebroside (Gal-C)], ECM markers [tenascin-C (TN-C), chondroitin sulfate, a chondroitin sulfate proteoglycan termed dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG)], stem-cell marker (nestin), and proliferation-specific marker [bromodeoxyuridine (BrdU)]. TuJ1+ and nestin+ cells (neurons and stem cells, respectively) persist in the region into adulthood, although the numbers of these cells become more sparse as the animal develops, and they appear to be immature compared to the cells in surrounding forebrain structures (e.g., not expressing NSE and having few, if any, processes). Likewise, NADPH-d+ cells are found in and around the SVZ during early postnatal development but become more sparse in the proliferative zone through maturity, and, by adulthood, only a few labeled cells can be found at the border between the SVZ and surrounding forebrain structures (e.g., the striatum), and even smaller numbers of positive cells can be found within the adult SVZ proper. BrdU labeling also seems to decrease significantly after the first postnatal week, but it still persists in the SVZ of adult animals. The disappearance of RC-2+ (radial) glia during postnatal development and the persistence of glial-derived ECM molecules such as tenascin and chondroitin sulfate proteoglycans (as well as other "boundary" molecules) in the adult SVZ may be associated with a persistence of immaturity, cell death, and a lack of cell emigration from the SVZ in the adult.
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PMID:Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres. 854 61

The subependymal zone (SEZ) of the lateral ventricle of adult rodents has long been known to be mitotically active. There has been increased interest in the SEZ, since it has been demonstrated that neuroepithelial stem cells residing there generate neurons in addition to glia in vitro. In the present study, we have examined parasagittal sections of the adult mouse brain using immunocytochemistry for extracellular matrix (ECM) molecules (tenascin and chondroitin sulfate-containing proteoglycans), glial fibrillary acidic protein (GFAP, a cytoskeletal protein prominently expressed by immature and reactive astrocytes), RC-2 (a radial glial and immature astrocyte cytoskeletal marker), TuJ1 (a class III beta-tubulin isoform expressed solely by postmitotic and adult neurons), nestin (a cytoskeletal protein associated with stem cells), neuron-specific enolase, and bromodeoxyuridine (BrdU, which is taken up by dividing cells). Our results demonstrate that a population of young neurons reside within an ECM-rich, GFAP-positive astrocyte pathway from the rostral SEZ all the way into the olfactory bulb. Furthermore, BrdU labeling studies indicate that there is a high level of cell division along the entire length of this path, and double-labeling studies indicate that neurons committed to a neuronal lineage (i.e., TuJ1+) take up BrdU (suggesting they are in the DNA synthesis phase of the cell cycle), again along the entire length of the SEZ "migratory pathway." Thus, the SEZ appears to retain the ability to produce neurons and glia throughout the life of the animal, functioning as a type of "brain marrow." The implications of these findings are discussed in relation to the role that such a glial/ ECM-rich boundary (as seen in the embryonic cortical subplate and other developing areas) may play in: confining the migratory populations and maintaining them in a persistent state of immaturity; facilitating their migration to the olfactory bulb, where they are incorporated into established adult circuitries; and potentially altering SEZ cell cycle dynamics that eventually lead to cell death.
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PMID:Young neurons from the adult subependymal zone proliferate and migrate along an astrocyte, extracellular matrix-rich pathway. 872 38

Classically, bone marrow mesenchymal stem cells (MSC) differentiate in vivo or in vitro into osteocytes, chondrocytes, fibroblasts and adipocytes. Recently, it was reported by several groups that MSC can also adopt a neural fate in appropriate in vivo or in vitro experimental conditions. However, it is unclear if those cells are really able to differentiate into functional neural cells and in particular into functional neurons. Some observations suggest that a cell fusion process underlies the neural fate adoption by MSC in vivo and first attempts to reproduce in vitro this neural fate decision in MSC cultures were unsuccessful. More recently, however, in several laboratories including ours, differentiation of MSC cultivated from adult rat bone marrow into astrocytes and neuron-like cells was demonstrated. More precisely, we stressed the importance of the expression by MSC of nestin, an intermediate filament protein associated with immaturity in the nervous system, as a pre-requisite to adopting an astrocytic or a neuronal fate in a co-culture paradigm. Using this approach, we have also demonstrated that the MSC-derived neuron-like cells exhibit several electrophysiological key properties classically devoted to neurons, including firing of action potentials. In this review, we will discuss the neurogenic potential of MSC, the factor(s) required for such plasticity, the molecular mechanism(s) underlying this neural plasticity, the importance of the environment of MSC to adopt this neural fate and the therapeutic potential of these observations.
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PMID:Astrocytic and neuronal fate of mesenchymal stem cells expressing nestin. 1632 9

Neural components in mature teratomas are common and the general assumption is that they are quite similar to those in the mature central nervous system (CNS). We investigated 44 ovarian teratomas by immunohistochemistry to determine cellular and structural immaturity of neural elements. Most teratomas contained cells differentiating into astrocytes positive for nestin, a neural stem cell marker. These nestin-positive astrocytes generally co-expressed glial fibrillary acidic protein-delta, an immature astrocyte marker. Olig2-positive cells were randomly scattered. Areas comprising cells that differentiated into neurons were positive for NeuN and synaptophysin. The border between white and gray matter was ill-defined and more NeuN-positive cells were distributed in areas that were positive for myelin basic protein, indicating that the distribution of neurons and glial cells was disturbed. Peripheral nerve bundles positive for Schwann/2E, an antigen specific for myelinating Schwann cells, were mixed within CNS-like tissues. These results show that apparently mature teratomas are not in fact mature, at least in terms of neural elements, as they harbor immature cells and structural abnormalities. The neural elements of surgically resected teratomas might represent a premature state of the human CNS, and thus be potentially useful for studies of developmental neurobiology as well as gliomagenesis.
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PMID:Immunophenotypic features of immaturity of neural elements in ovarian teratoma. 2663 57

Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans through activation of the hypothalamic Jak-STAT (Janus kinase-signal transducer and activator of transcription) signaling pathway. Here, we tested the hypothesis that CNTF also affects the brainstem centers involved in feeding and energy balance regulation. To this end, wild-type and leptin-deficient (ob/ob and db/db) obese mice were acutely treated with intraperitoneal recombinant CNTF. Coronal brainstem sections were processed for immunohistochemical detection of STAT3, STAT1, STAT5 phosphorylation and c-Fos. In wild-type mice, CNTF treatment for 45 min induced STAT3, STAT1, and STAT5 phosphorylation in neurons as well as glial cells of the area postrema; here, the majority of CNTF-responsive cells activated multiple STAT isoforms, and a significant proportion of CNTF-responsive glial cells bore the immaturity and plasticity markers nestin and vimentin. After 120 min CNTF treatment, c-Fos expression was intense in glial cells and weak in neurons of the area postrema, it was intense in several neurons of the rostral and caudal solitary tract nucleus (NTS), and weak in some cholinergic neurons of the dorsal motor nucleus of the vagus. In the ob/ob and db/db mice, Jak-STAT activation and c-Fos expression were similar to those induced in wild-type mouse brainstem. Treatment with CNTF (120 min, to induce c-Fos expression) and leptin (25 min, to induce STAT3 phosphorylation) demonstrated the co-localization of the two transcription factors in a small neuron population in the caudal NTS portion. Finally, weak immunohistochemical CNTF staining, detected in funiculus separans, and meningeal glial cells, matched the modest amount of CNTF found by RT-qPCR in micropunched area postrema tissue, which in contrast exhibited a very high amount of CNTF receptor. Collectively, the present findings show that the area postrema and the NTS exhibit high, distinctive responsiveness to circulating exogenous and, probably, endogenous CNTF.
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PMID:Action of Administered Ciliary Neurotrophic Factor on the Mouse Dorsal Vagal Complex. 2744 62

Colorectal cancer is the third most commonly diagnosed cancer in males and the second most common in females. Only 10-20% of patients are diagnosed at the early stage of disease. Recently, the role of novel biomarkers of the neoplastic process in the early detection of colorectal cancer has been widely discussed. In this review, we focused on the three novel biomarkers that are of potential clinical importance in diagnosing and monitoring colorectal cancer. Chitinase 3-like 1 protein, also known as YKL-40, and nestin and testin proteins are produced by colorectal cancer cells. YKL-40 protein is a marker of proliferation, differentiation, and tissue morphogenetic changes. The level of YKL-40 is elevated in about 20% of patients with colorectal cancer. An increased expression of nestin indicates immaturity. It is a marker of angiogenesis in neoplastic processes. Testin protein is a component of cell-cell connections and focal adhesions. The protein is produced in normal human tissues, but not in tumor tissues. Downregulation of testin increases cell motility, spread, and proliferation, and decreases apoptosis. The usefulness and role of these biomarkers, both alone and combined, in the diagnostics of colorectal cancer should be further explored as early cancer detection may substantially improve treatment outcome and patient survival.
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PMID:Chitinase 3-Like 1, Nestin, and Testin Proteins as Novel Biomarkers of Potential Clinical Use in Colorectal Cancer: A Review. 3217 Jun 69