PubMed Health⌕ Search

Biomedical subjects

R Devon

Publications and source records attributed to R Devon.

6 recordsLinked to original sources
PubMed1998

Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates.

It is unclear how polyglutamine expansion is associated with the pathogenesis of Huntington disease (HD). Here, we provide evidence that polyglutamine expansion leads to the formation of large intracellular aggregates in vitro and in vivo. In vitro these huntingtin-containing aggregates disrupt normal cellular architecture and increase in frequency with polyglutamine length. Huntingtin truncated at nucleotide 1955, close to the caspase-3 cleavage site, forms perinuclear aggregates more readily than full-length huntingtin and increases the susceptibility of cells to death following apoptotic stimuli. Further truncation of huntingtin to nucleotide 436 results in both intranuclear and perinuclear aggregates. For a given protein size, increasing polyglutamine length is associated with increased cellular toxicity. Asymptomatic transgenic mice expressing full-length huntingtin with 138 polyglutamines form exclusively perinuclear aggregates in neurons. These data support the hypothesis that proteolytic cleavage of mutant huntingtin leads to the development of aggregates which compromise cell viability, and that their localization is influenced by protein length.

Animals↗
PubMed1995

Olfactory ensheathing cells do not require L-ascorbic acid in vitro to assemble a basal lamina or to myelinate dorsal root ganglion neurites.

Ensheathing cells reside within both the PNS and CNS portions of the primary olfactory pathway and provide a glial covering and support for the unmyelinated olfactory axons. In vivo, these ensheathing cells express a mixture of astrocyte-specific and Schwann cell-specific phenotypic features. When grown in vitro in the presence of DRG neurons however, these ensheathing cells were observed to myelinate DRG neurites. The purpose of the present study was to determine whether ensheathing cells, like Schwann cells, require the addition of ascorbic acid to the medium in order to assemble a basal lamina and a myelin sheath. Our findings indicate that ensheathing cells can myelinate DRG neurites regardless of whether ascorbic acid is included in the growth medium and that these glial cells can assemble a basal lamina in the absence of added ascorbic acid. It appears from these results that Schwann cells and ensheathing cells have different growth media requirements for the assembly of a basal lamina.

Animals↗
PubMed1995

Elevated intracellular levels of cAMP induce olfactory ensheathing cells to express GAL-C and GFAP but not MBP.

The primary olfactory pathway contains non-myelinating glial cells, called ensheathing cells, that exhibit a variety of phenotypes depending on their immediate environment. In vivo, these cells normally possess a mixture of astrocyte- and Schwann cell-specific phenotypic features. When co-cultured with dorsal root ganglion neurons, their phenotype can become more like that of a myelinating Schwann cell. The objective of this study was to determine whether ensheathing cells would express a myelinating phenotype in culture in the absence of neurons but in the presence of cAMP analogues that are known to induce the expression of myelin associated molecules in Schwann cell cultures. The ensheathing cell cultures were initiated using the nerve fiber layers of Theiler stage 23 rat olfactory bulb primordia and were fed for 1 day to 3 weeks with serum containing (1% or 10% FBS) or serum-free media to which was added different concentrations of dBcAMP (0.1 to 1 mM) or forskolin (10 microM). These cultures were double-labelled with a rabbit polyclonal antibody to S100 in combination with mouse anti-GAL-C (O1 and BRD1 hybridomas) or anti-MBP monoclonal antibodies. The remaining cultures were double-labeled with a rabbit polyclonal antibody to GFAP in combination with the BRD1 antibody. Treatment with dBcAMP or forskolin failed to induce ensheathing cells to express MBP regardless of the concentration. On the other hand, the treatment induced approximately one tenth of the cells to express GAL-C, and virtually all of the cells to express GFAP. These results indicate that although ensheathing cells can synthesize myelin associated molecules, the cAMP second messenger system appears to play a lesser role in controlling the expression of a myelinating phenotype in ensheathing cells than it does in Schwann cells.

Animals↗
PubMed1994

Media that support the growth and differentiation of oligodendrocytes do not induce olfactory ensheathing cells to express a myelinating phenotype.

The glial cells that ensheath olfactory axons are referred to as ensheathing cells. In vivo, these non-myelinating glial cells express a mixture of astrocyte-specific and Schwann cell-specific phenotypic features with the former cellular phenotype predominating, but in vitro can assemble a myelin sheath when co-cultured with dorsal root ganglion neurons. Thus, certain in vitro conditions induce ensheathing cells to express a phenotype more like that of a myelinating Schwann cell. The present study addresses whether ensheathing cells will express a myelinating phenotype in neuron-free cultures when fed for 1 to 5 weeks with media shown to promote the growth and differentiation of oligodendrocyte progenitor cells. The ensheathing cell cultures were initiated using the nerve fiber layers (NFL) of rat olfactory bulb primordia. Oligodendrocyte cultures were established from newborn rat neopallium and from the tissue that remained after removing the NFL from the developing olfactory bulb (i.e., the OB-NFL). The cultures were double-labelled with rabbit polyclonal antibodies to S100 or glial fibrillary acidic protein in combination with the mouse monoclonal antibodies O4, BRD1 [anti-galactocerebroside (anti-GAL-C)], and anti-myelin basic protein (MBP). In some experiments the ensheathing cells were labelled with PKH26 prior to being co-cultured with oligodendrocytes of the OB-NFL. None of the media induced ensheathing cells to express either GAL-C or MBP. However, when 0.5 mM dibutyrylcyclic-AMP (dBcAMP) was added to the medium, ensheathing cells became GAL-C + ve, but remained MBP-ve. The molecular mechanisms that regulate the expression of a myelinating phenotype by ensheathing cells appear to be different from those that operate in oligodendrocytes.

Animals↗
PubMed1992

Olfactory ensheathing cells myelinate dorsal root ganglion neurites.

The objective of this study was to determine whether olfactory ensheathing cells (from E18 rat embryos) could myelinate dorsal root ganglion neurites in vitro. By four weeks many of the S100-positive ensheathing cells were Gal-C+ and MBP+ and had begun to myelinate the larger axons, as visualized with the electron microscope. We conclude that olfactory ensheathing cells can form a myelin sheath if given the opportunity to ensheath neurites of a proper size.

Animals↗