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Biomedical subjects

J F Diedrich

Publications and source records attributed to J F Diedrich.

5 recordsLinked to original sources
PubMed1993

Increased expression of heat shock protein, transferrin, and beta 2-microglobulin in astrocytes during scrapie.

Scrapie is a slow infection and neurodegenerative disease of animals characterized pathologically by formation of amyloid, astrocytosis, vacuolation and injury and death of neurons. Our previous studies of scrapie point to: (i) a critical role for the astrocyte in responding to, and perhaps inadvertently contributing to, the neuropathological manifestations of infection; and (ii), the hypothesis that the astrocyte executes a programed response to neurological injury analogous to the stress response. The expression of genes encoding transferrin and beta 2-microglobulin has been shown to increase during scrapie and we sought in the studies reported here to determine whether this modulated expression would map to astrocytes. We also looked for changes in a heat shock protein that is induced in the stress response. We show that transferrin, beta 2-microglobulin and heat shock 72 kD protein all increase in astrocytes in the course of infection. We speculate in the discussion on the possible functions of these and other proteins in neurodegenerative processes and why these functions so frequently reside in the astrocyte.

Animals↗
PubMed1991

Scrapie-associated prion protein accumulates in astrocytes during scrapie infection.

In the course of scrapie, a transmissible spongiform encephalopathy caused by an unconventional agent, a normal cellular protein is converted to an abnormal form that copurifies with infectivity and aggregates to form deposits of amyloid. We have used immunocytochemistry and methods that enhance detection of amyloidogenic proteins to investigate the types of cells in the central nervous system which are involved in the formation of the abnormal scrapie-associated protein. We show that this protein accumulates in astrocytes prior to the cardinal neuropathological changes in scrapie--astrogliosis, vacuolation, neuron loss, and amyloid deposition. These findings implicate the astrocyte in the formation of the scrapie isoform of the prion protein and amyloid in scrapie and suggest that this cell type might also be involved in the replication of the scrapie agent.

Amyloid↗
PubMed1991

Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes.

With the rationale that the neuropathological similarities between scrapie and Alzheimer's disease reflect convergent pathological mechanisms involving altered gene expression, we set out to identify molecular events involved in both processes, using scrapie as a model to study the time course of these changes. We differentially screened a cDNA library constructed from scrapie-infected mice to identify mRNAs that increase or decrease during disease and discovered in this way two mRNAs that are increased in scrapie and Alzheimer's disease. These mRNAs were subsequently shown by sequence analysis to encode apolipoprotein E and cathepsin D (EC 3.4.23.5). Using in situ hybridization and immunocytochemistry to define the cellular and anatomic pathology of altered gene expression, we found that in both diseases the increase in apolipoprotein E and cathepsin D mRNAs and proteins occurred in activated astrocytes. In scrapie, the increase in gene expression occurred soon after the amyloid-forming abnormal isoform of the prion protein has been shown to accumulate in astrocytes. In Alzheimer's disease, the increased expression of cathepsin D also occurred in association with beta-amyloid. These studies reveal some of the molecular antecedents of neuropathological changes in scrapie and Alzheimer's disease and accord new prominence to the role of astrocytes in neurodegenerative conditions.

Aged↗