Neurosteroids alter glutamate-induced changes in neurite morphology of NG108-15 cells. 2007

Tobias Johansson, and Martin Elfverson, and Carolina Birgner, and Per-Anders Frändberg, and Fred Nyberg, and Pierre Le Grevès
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, S-751 24 Uppsala, Sweden.

Activation of the NMDA receptor leads to increased intracellular Ca2+ levels ([Ca2+]i) which induces outgrowth of and morphologic changes in the neurites of the NG108-15 cell line. This effect can be blocked by antagonists for this glutamate receptor subtype (e.g. ifenprodil or AP5). We have previously shown that nanomolar concentrations of various neurosteroids modulate ifenprodil binding to the NMDA receptor. To investigate whether this interaction affects the functioning of the receptor, we studied the effect of 24 and 48 h of pregnenolone sulphate (PS) or pregnanolone sulphate (3alpha5betaS) on glutamate-stimulated NG108-15 cells. Unexpectedly, the neurosteroids themselves had an inhibitory effect on glutamate-induced changes in neurite patterns. This effect was comparable to that of ifenprodil or AP5. Moreover, the effect of combined treatment with 3alpha5betaS and ifenprodil on neurite morphology indicated a functional interaction between the substances. Interestingly, PS induced cell detachment over time, an effect that was further enhanced by ifenprodil. Cell detachment was also seen after 48 h of treatment with 3alpha5betaS; however, the effect was blocked by ifenprodil and weaker than that of PS. The interaction with the NR2B-selective antagonist ifenprodil indicates that this NMDA receptor subunit may be involved in neurosteroid-induced NG108-15 cell detachment.

UI MeSH Term Description Entries
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D010880 Piperidines A family of hexahydropyridines.
D011284 Pregnenolone A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS. 5-Pregnen-3-beta-ol-20-one,5 Pregnen 3 beta ol 20 one
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D005910 Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21) Glial Cell Tumors,Malignant Glioma,Mixed Glioma,Glial Cell Tumor,Glioma, Malignant,Glioma, Mixed,Gliomas,Gliomas, Malignant,Gliomas, Mixed,Malignant Gliomas,Mixed Gliomas,Tumor, Glial Cell,Tumors, Glial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006822 Hybrid Cells Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION. Somatic Cell Hybrids,Cell Hybrid, Somatic,Cell Hybrids, Somatic,Cell, Hybrid,Cells, Hybrid,Hybrid Cell,Hybrid, Somatic Cell,Hybrids, Somatic Cell,Somatic Cell Hybrid
D013256 Steroids A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed) Steroid,Catatoxic Steroids,Steroids, Catatoxic
D015763 2-Amino-5-phosphonovalerate The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors. 2-Amino-5-phosphonopentanoic Acid,2-Amino-5-phosphonovaleric Acid,2-APV,2-Amino-5-phosphonopentanoate,5-Phosphononorvaline,d-APV,dl-APV,2 Amino 5 phosphonopentanoate,2 Amino 5 phosphonopentanoic Acid,2 Amino 5 phosphonovalerate,2 Amino 5 phosphonovaleric Acid,5 Phosphononorvaline
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate

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