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Biomedical subjects

M Oberto

Publications and source records attributed to M Oberto.

5 recordsLinked to original sources
PubMed2001

ErbB-4 and neuregulin expression in the adult mouse olfactory bulb after peripheral denervation.

ErbB-4 is expressed by the periglomerular and the mitral/tufted cells of the adult mouse olfactory bulb (OB) and in the present work we tested whether this expression is regulated by the olfactory nerve input to the OB. Reversible zinc sulphate lesions of the olfactory mucosa were made in adult mice and the deafferented OB analysed by immunohistochemistry, Western blotting and semiquantitative RT-PCR. Following deafferentation, the expression of erbB-4, erbB-2 and neuregulin-1 (NRG-1) mRNAs in the OB was altered. At early stages (7-14 days) after lesion the levels of expression of olfactory marker protein (OMP), tyrosine hydroxylase (TH), erbB-4 and NRG-1 mRNAs were decreased, whilst expression of erbB-2 increased and that of NRG-2 was not significantly altered. We observed at least two distinct time courses for these expression changes. The lowest amounts of mRNA for erbB-4 and NRG-1 were observed at day 7 after lesion, whilst mRNAs for TH and OMP were lowest at day 14. At day 28 after the lesion, when olfactory receptor neuron axons had reinnervated the olfactory bulb, the expression levels of OMP, TH, erbB-2, erbB-4 and NRG-1 were identical to control values. These results indicate that the expression of erbB-4 mRNA and protein in periglomerular and mitral cells is controlled by peripheral olfactory innervation. The tight correlation in NRG-1 and erbB-4 expression levels also suggests a possible functional link that deserves further exploration.

Animals↗
PubMed1999

Transregulation of erbB expression in the mouse olfactory bulb.

Previously, we have shown that erbB-3 expression is restricted to the ensheathing cells of the olfactory nerve layer, while erbB-4 is found in the periglomerular and mitral/tufted cells of the olfactory bulb and in cells coming out from the rostral migratory stream of the subependymal layer. In the present work, we have treated adult mice with zinc sulfate intranasal irrigation and analyzed erbB-3 and erbB-4 expression in the deafferented olfactory bulb. Following treatment, olfactory axons undergo degeneration, as indicated by the loss of OMP expression in the deafferented olfactory bulb. The thickness of the olfactory nerve layer is reduced, but the specific intensity of erbB-3 labeling in the remaining olfactory nerve layer is increased with respect to control. Interestingly, following deafferentation, erbB-4 immunoreactivity decreases specifically in cell types that normally make synaptic contacts with primary olfactory neurons in the glomeruli, i.e. periglomerular and mitral/tufted cells. Partial lesion of the olfactory epithelium allows regenerative axon growth of olfactory neurons to the olfactory bulb. Following olfactory axon regeneration, erbB-3 and erbB-4 immunoreactivity in the olfactory bulb is similar to control. Thus, like tyrosine hydroxylase, the down regulation of erbB-4 expression in the periglomerular cells is reversible.

Administration, Intranasal↗
PubMed1998

ErbB-3 and ErbB-4 expression in the mouse olfactory system.

The interplay between neuregulins and the ErbB receptor family has a pivotal role in the development of several tissues, including the nervous system, and is maintained in the adult olfactory system where extensive plasticity and neurogenesis are retained. In the present work we show the immunohistochemical localization of ErbB-3 and ErbB-4 in the olfactory system of adult normal and lesioned mice. The expression of ErbB-3 is demonstrated to be restricted to the ensheathing cells of the olfactory nerve and to a few substentacular cells of the olfactory epithelium (OE). ErbB-3 staining circumvents the glomeruli but is never observed inside them or elsewhere in the adult olfactory bulb. Conversely, ErbB-4 immunoreactivity is found in all the periglomerular and mitral/tufted cells of the olfactory bulb (OB) and to a minor extent in the olfactory neurons and basal cells of the OE. Interestingly enough, cells coming out from the rostral migratory stream of the subependymal layer (SEL), as well as isolated cells in the granule cell layer, possibly migrating cells, strongly stained for ErbB-4 expression. Lesions of the olfactory epithelium have been performed by unilateral intranasal irrigation with ZnSO4 and 3 weeks after the irrigation, the olfactory bulbs were analyzed for olfactory marker protein (OMP), tyrosine hydroxylase (TH), ErbB-3 and ErbB-4 expression. In the deafferented OB, the drastic loss of immunoreactivity for OMP was accompanied by a strong reduction of ErbB-3 expression. Most of the deafferented dopaminergic interneurons switched off TH expression. In the deafferented periglomerular and mitral/tufted cells ErbB-4 expression was turned off and down, respectively. No differences were noted at the granular cell layer level in the deafferented OB with respect to control. Taken together our results suggest that, in normal conditions, neuregulins are involved in the survival of the ensheathing cells of the olfactory nerve through ErbB-3 activation and in the functional activity of postsynaptic neurons through ErbB-4 activation.

Animals↗
PubMed1998

Resistance of t(4;11) (MLL-AF4 fusion gene) leukemias to stress-induced cell death: possible mechanism for extensive extramedullary accumulation of cells and poor prognosis.

Acute leukemias of the t(4;11) (MLL-AF4 fusion gene) type frequently have high white blood counts and extramedullary disease in multiple organs. In the present study we evaluated the hypotheses that this extensive disease is the result of extramedullary survival of leukemia cells due to resistance to stress-induced cell death. Leukemias with t(4;11)(MLL-AF4) were found to be resistant to the cell death that results from serum deprivation in vitro when compared with B lineage acute leukemias without t(4;11)(MLL-AF4). Cells with t(4;11)(MLL-AF4) did not have increased doubling time or increased numbers of cells in cycle. These results suggest that the alteration in cellular homeostasis in these leukemias is due to abnormalities of cellular destruction rather than cellular proliferation when compared to other leukemias. Our results are consistent with the hypothesis that death of non-t(4;11) leukemias occurs in the microenvironment outside of the bone marrow as a result of deficient cellular and humoral growth factors. Resistance to death signals in t(4;11) leukemias results in extensive accumulation of leukemia cells in extramedullary sites and likely contributes to the poor prognosis of these leukemias.

Artificial Gene Fusion↗