Biomedical subjects

David H Hall

Publications and source records attributed to David H Hall.

22 records · Page 2Linked to original sources

PubMed2002

Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60-100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.

Aging↗

PubMed2002

Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans.

Parkinson's disease is a complex neurodegenerative disorder characterized by the death of brain dopamine neurons. In mammals, dopamine neuronal degeneration can be triggered through exposure to neurotoxins accumulated by the presynaptic dopamine transporter (DAT), including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium. We have established a system for the pharmacological and genetic evaluation of neurotoxin-induced dopamine neuronal death in Caenorhabditis elegans. Brief (1 h) exposure of green fluorescent protein-tagged, living worms to 6-OHDA causes selective degeneration of dopamine neurons. We demonstrate that agents that interfere with DAT function protect against 6-OHDA toxicity. 6-OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT.

Animals↗

PubMed2002

Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization.

During development, neurons extend axons along defined routes to specific target cells. We show that additional mechanisms ensure that axons maintain their correct positioning in defined axonal tracts. After termination of axonal outgrowth and target recognition, axons in the ventral nerve cord (VNC) of Caenorhabditis elegans require the presence of a specific VNC neuron, PVT, to maintain their correct positioning in the left and right fascicles of the VNC. PVT may exert its stabilizing function by the temporally tightly controlled secretion of 2-immunoglobulin (Ig)-domain proteins encoded by the zig genes. Dedicated axon maintenance mechanisms may be widely used to ensure the preservation of functional neuronal circuitries.

Animals↗

PubMed2002

Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in invertebrate neurons.

The endoplasmic reticulum (ER) is divided into rough and smooth domains (RER and SER). The two domains share most proteins, but RER is enriched in some membrane proteins by an unknown mechanism. We studied RER protein targeting by expressing fluorescent protein fusions to ER membrane proteins in Caenorhabditis elegans. In several cell types RER and general ER proteins colocalized, but in neurons RER proteins were concentrated in the cell body, whereas general ER proteins were also found in neurites. Surprisingly RER membrane proteins diffused rapidly within the cell body, indicating they are not localized by immobilization. Ribosomes were also concentrated in the cell body, suggesting they may be in part responsible for targeting RER membrane proteins.

Animals↗