title: Subacute necrotizing encephalopathy in a pig-tailed macaque (Macaca nemestrina) that resembles mitochondrial encephalopathy in humans.
abstract: A male pig-tailed macaque (Macaca nemestrina), approximately 5 years old, was found to be vision-impaired and to have profound behavioral abnormalities, including hyperactivity and self-injurious behavior that was not amenable to amelioration by environmental enrichment. Facial and skeletal dysmorphisms also were noted. Magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning revealed areas of possible infarction in the occipital lobes and megaventriculosis. At necropsy, following euthanasia for humane reasons, severe polio- and leukoencephalomalacia accompanied by megaventriculosis were seen in both occipital lobes and in several sulci of the parietal and frontal lobes. Light microscopic findings included loss of neocortical structure, with necrosis, neuronal loss, astrogliosis, vascular proliferation, mild spongiosis, and demyelination. The extent and severity of lesions were most pronounced in the occipital lobes and were greater in the left than in the right hemisphere. Other lesions included mild bilateral atrophy of the optic nerves, thymic involution, necrotizing dermatitis due to trauma, and a spectrum of spermatozoal abnormalities. The imaging and gross and light microscopic changes found in this animal resemble the mitochondrial encephalopathies of humans; this was corroborated by results of immunohistochemical analysis demonstrating decreased expression of enzymes of the mitochondrial oxidative complex ([OC]-I, -III, and -IV) in brain and muscle, and detection of fibrinogen immunoreactivity in neurons and glial cells. The spermatozoal defects may represent yet another aspect of a mitochondrial defect.
authors.affiliation: Washington National Primate Research Center, University of Washington, Seattle, Washington 98195-7330, USA.
authors.forename: Helle
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.forename: Rita U
authors.initials: RU
authors.lastname: Bellanca
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Crockett
authors.forename: Eliza
authors.initials: E
authors.lastname: Curnow
authors.forename: Kathy
authors.initials: K
authors.lastname: Eiffert
authors.forename: Maggie
authors.initials: M
authors.lastname: Gillen
authors.forename: Debra
authors.initials: D
authors.lastname: Glanister
authors.forename: Eric
authors.initials: E
authors.lastname: Hayes
authors.forename: Stephen
authors.initials: S
authors.lastname: Kelley
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.forename: Keith
authors.initials: K
authors.lastname: Vogel
mesh_terms: D000818:Animals; D000830:Animals, Laboratory; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007888:Leigh Disease / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D008254:Macaca nemestrina; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D008992:Monkey Diseases / Q000473:pathology / Q000503:physiopathology; D013094:Spermatozoa / Q000002:abnormalities / Q000378:metabolism