Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Cholinergic axonal dystrophy and mitochondrial pathology in prosimian primates.

D E Schmechel; D S Burkhart; R Ange; M K Izard (Profiled Author: Schmechel, Donald E)

Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 22710, USA.
Experimental neurology 1996;142(1):111-27.

Progressive cholinergic axonal dystrophy, cholinergic denervation, and generalized gliosis begin in the prosimian primate species Otolemur at 10% of maximum life span. In these same animals, extensive cerebral beta-amyloidosis follows relatively more abruptly at 50% of maximum life span. In contrast, even at maximum life span, the prosimian primate species Galago senegalensis Moholi, Microcebus murinus, and Eulemur fulvus collaris and insectivore species T. belangeri are either spared or much less affected. In this report, we further document this progressive cholinergic denervation in Otolemur which involves first projections of the pedunculopontine nucleus (PPN, CH5-6) and later projections of CH1-4 cholinergic nuclei, as well as other noncholinergic pathways. Affected cholinergic cell bodies and axons contain abnormal mitochondria with increased content of manganese superoxide dismutase (MnSOD). This syndrome correlates with moderate copper deficiency marked by diminished liver copper levels and cuproenzyme activities, carnitine deficiency possibly secondary to renal Fanconi syndrome, and evidence for stress inflammatory response activation. Mitochondrial pathology was observed in pancreatic islet cells, proximal renal tubule epithelial cells, and choroid plexus epithelial cells, and it involved central cholinergic neurons. In Otolemur garnetti, the degree of central cholinergic injury directly correlated to depression of liver copper stores. The Otolemur syndrome involves "sentinel" central cholinergic injury and selective mitochondrial pathology in cell classes defined by high mitochondrial content and/or metabolic activity and high content of nitric oxide synthetase and MnSOD. Environmental factors affecting copper and carnitine metabolism could interact with genetic defects or traits to produce abnormal and aggressive aging of Otolemur. Subclinical, cell-class specific mitochondrial dysfunction in these prosimian primates may be a model for human neurodegenerative diseases.

2 Originating Grant

• 1.

  Schmechel, Donald E

  ALZHEIMER'S DISEASE RESEARCH CENTER

  1 May 2000 - 30 April 2005

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 16,537,307

• 2.

  ROSES, ALLEN D

  ALZHEIMERS DISEASE RESEARCH CENTER

  30 September 1985 - 30 April 2000

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 17,660,528

Scientific Context

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