Impaired adult neurogenesis associated with short-term memory defects in NF-kappaB p50-deficient mice.

Neurogenesis proceeds throughout adulthood in the brain of most mammalian species, but the molecular mechanisms underlying the regulation of stem/progenitor cell proliferation, survival, maturation, and differentiation have not been completely unraveled. We have studied hippocampal neurogenesis in NF-kappaB p50-deficient mice. Here we demonstrate that in absence of p50, the net rate of neural precursor proliferation does not change, but some of the steps leading to the final neuron differentiation status are hampered, resulting in approximately 50% reduction in the number of newly born neurons in the adult mutant hippocampus.

Members of the NF-kappaB family expressed in zones of active neurogenesis in the postnatal and adult mouse brain.

The Rel/NF-kappaB family of transcription factors is implicated in cell proliferation, cell death, cell migration and cell interactions. Here, we examined by immunohistochemistry the expression pattern of various members of this family during postnatal telencephalon development and during adulthood, and we used neuronal and glial markers to identify the cells types where they are expressed. Distinct Rel/NF-kappaB proteins are highly expressed postnatally in the subventricular zone and in the rostral migratory stream.

Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation.

Microglial cells are non-professional antigen-presenting cells (APC) the function of which is still controversial. Here, we studied the function of microglia derived from H-2(u) mice. We show that these microglia express a low level of B7.

Localization of calcitonin gene-related peptide mRNA in developing olfactory axons.

During development of the olfactory pathway, calcitonin gene-related peptide (CGRP) expression is regulated both temporally and spatially. We had previous evidence that between E13 and E19 CGRP mRNA was present at the level of olfactory axons but the resolution of light-microscope in situ hybridization did not permit the axons to be distinguished from the closely apposed ensheathing cells. In this study, the localization of CGRP mRNA was studied at early developmental stages (E13-15) through in situ hybridization at the transmission electron-microscope (TEM) level.

Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells.

The t(8;21) translocation associated with acute myeloid leukemia (AML) disrupts two genes, the AML1 gene also known as the core binding factor A2 (CBFA2) on chromosome 21, and a gene on chromosome 8, hereafter referred to as MTG8, but also known as CDR and ETO. Extensive information is available on AML1, a member of the CBF family of transcription factors, containing a highly conserved domain, the runt box, of the Drosophila segmentation gene runt. This gene is essential for the hematopoietic development and is found disrupted in several leukemias.

The Ras Guanine nucleotide Exchange Factor CDC25Mm is present at the synaptic junction.

CDC25Mm, a mouse Ras-Guanine nucleotide Exchange Factor, is specifically expressed as a product of 140 kDa (p140) in the postnatal and adult brain. Immunohistochemical analysis indicates that it is present throughout the brain particularly concentrated in discrete punctate structures. Subcellular fractionation of the mouse brain shows that p140 is present in synaptosomes but not in highly purified synaptic vesicles.

Differential regulation of indoleamine 2,3-dioxygenase expression by nitric oxide and inflammatory mediators in IFN-gamma-activated murine macrophages and microglial cells.

Induction of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) is involved in the immunomodulatory roles of IFN-gamma and evidence suggests that these pathways are functionally cross-regulated. We report here that nitric oxide (NO) negatively modulates the expression of IDO activity in IFN-gamma-primed macrophages, but not in microglial cells from mouse. In MT2 macrophages, the induction of IDO activity by IFN-gamma was further increased by the presence of NOS inhibitors, whereas culturing of IFN-gamma-activated MT2 cells with NO generators produced a marked reduction of IDO activity expression.

Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro.

Neuronal proliferation, migration, and differentiation are regulated by the sequential expression of particular genes at specific stages of development. Such processes rely on differential gene expression modulated through second-messenger systems. Early postnatal mouse cerebellar granule cells migrate into the internal granular layer and acquire differentiated properties.

Cloned microglial cells but not macrophages synthesize beta-endorphin in response to CRH activation.

The properties of microglial cell clones, obtained from embryonic mouse brain primary cultures immortalized with recombinant retroviruses, have been investigated and compared with the properties of macrophage clones similarly obtained. Macrophage clones differed from microglial clones in some functions but shared most of the immunological properties. Interestingly, microglial cells were able to produce beta-endorphin, and this production was regulated differently in microglial cell clones when compared with macrophages clones.

Developmentally regulated expression of CGRP in the mouse olfactory pathway.

The pattern of expression of the neuropeptide CGRP and its encoding mRNA has been determined by immunohistochemistry and in situ hybridization in the mouse olfactory pathway during development. Specific CGRP transcripts are first detected at E13 followed by the appearance of the peptide at E15. Both peptide and transcript are present until birth; their expression then appears to be down-regulated since postnatally the peptide is only observed in some olfactory receptor neurons.

Expression of neurofilament proteins in granule cells of the cerebellum.

We have used a panel of monoclonal antibodies directed against the low, middle and high molecular weight subunits of neurofilament triplet, to study their expression in mouse cerebellar granule cells. We demonstrate that in situ such cells only express the 2 lower molecular weight subunits either at various developmental stages or in the adult. The same results were obtained in vitro.

Expression of dopaminergic phenotypes in the mouse olfactory bulb induced by the calcitonin gene-related peptide.

In the olfactory bulb, tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, is expressed after birth when the axons of olfactory epithelial neurons have made synapses in the bulb. It has been suggested that expression of TH is regulated trans-synaptically because on deafferentation of the bulb there is a marked decrease in the contents of TH, dopamine and 3,4-dihydroxyphenylacetic acid, which, however, return to normal levels after regeneration of the primary afferents. To date the molecular signalling involved in this trans-synaptic induction has not yet been characterized; I have therefore studied the expression of dopaminergic properties (presence of TH and dopamine uptake) in dissociated cell cultures from embryonic mouse olfactory bulb.

Human neuroblastoma cells acquire regulated secretory properties and different sensitivity to Ca2+ and alpha-latrotoxin after exposure to differentiating agents.

IMR-32 human neuroblastoma cells are unable to release [3H]dopamine in response to secretagogues. However, they express a normal complement of membrane receptors and ion channels which are efficiently coupled to second messenger production. In the present study we took advantage of the ability of this cell line to differentiate in vitro in the presence of either dibutyrryl-cAMP or 5-bromodeoxyuridine, to analyze any developmentally regulated changes in its secretory properties.

Interneurons versus efferent neurons: heterogeneity in their neurite outgrowth response to glia from several brain regions.

We have studied in vitro the morphology of two populations of dopaminergic neurons from mouse embryos: the periglomerular interneurons from the olfactory bulb (DOBI) and the efferent neurons from the substantia nigra (DENN). The intrinsic potential of both neuronal types has been studied by comparing process outgrowth in a predominantly neuronal environment or in a glial environment that is endogenous or from other brain regions. Both populations exhibit in vitro different characteristics that reflect their phenotype in situ.

Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus.

Stiff-man syndrome is a rare disorder of the central nervous system consisting of progressive, fluctuating muscle rigidity with painful spasms. It is occasionally associated with endocrine disorders, including insulin-dependent diabetes, and with epilepsy. We investigated the possible existence of autoimmunity against the nervous system in a patient with stiff-man syndrome associated with epilepsy and Type I diabetes mellitus.

Glial heterogeneity may define the three-dimensional shape of mouse mesencephalic dopaminergic neurones.

The shape of a neurone--the projection and branching pattern of axons and dendrites--appears to be determined by a combination of intrinisic and environmental influences. We have previously shown that striatal target neurones influence the biochemical maturation of ascending mesencephalic dopamine (DA) cells in culture, as well as the elongation rate of DA neurites. Using a similar approach in which the morphology of individual DA cells can be studied after 3H-DA uptake and autoradiography, we now report on in vitro neurone-glia interactions and show that glial cells exert a morphogenetic effect on DA neurones.

Calcium ultrastructural localization in Xenopus laevis eggs following activation by pricking or by calcium ionophore A 23187.

In the egg of Xenopus laevis a cortical network of smooth endoplasmic reticulum (SER) surrounds and interconnects each cortical granule (CG) (Campanella and Andreuccetti, '77). This network is a possible intracellular site of calcium storage to be called into action for CG exocytosis. In our experiments, Xenopus eggs, unfertilized or activated by pricking or by calcium ionophore A 23187, have been fixed in osmium-pyroantimonate for calcium localization.

Specific influence of striatal target neurons on the in vitro outgrowth of mesencephalic dopaminergic neurites: a morphological quantitative study.

In previous studies, we have shown that dissociated dopaminergic neurons from embryonic mouse in co-culture with striatal target neurons take up and synthesize dopamine to a greater extent. We now report that striatal target cells influence the morphology of dopaminergic neurons as well. In co-culture, the total length of neuritic arborization visualized by autoradiography is reduced when compared to cultures of mesencephalic neurons alone or to co-cultures with cerebellar cells.

Cell surface modifications in neuronal maturation.

Changes in carbohydrate composition of the cell surface related to neuronal maturation have been studied on neuroblastoma and embryonic dorsal root ganglia (DRG) cultures by using fluorescein conjugated lectins. In neuroblastoma cells, it has been found that the surface of the fibers differs from that of the cell body as shown by concanavalin A (Con A) and WGA binding. In primary cultures of embryonic DRG, lectin binding has also shown that the neuron surface undergoes changes during maturation.

[The effects of diverse agents (Ca++ and K++ ionophores, organomercurials, dithiols, colchicine, and cytochalasin B) on the maturation and differentiation without cleavage in Chaetopterus eggs].

Induction of maturation in Chaetopterus oocytes requires the presence of Ca++ ions in the medium, but differentiation without cleavage can proceed in the absence of this cation. The Ca++ ionophore A 23187 induces both maturation and the cortical reaction provided that Ca++ ions are present in the medium differentiation without cleavage may follow. Valinomycin slowly induces germinal vesicle breakdown, which is followed by a sharp segregation between hyaloplasm and yolk.