title: Lifelong expression of apolipoprotein D in the human brainstem: correlation with reduced age-related neurodegeneration.
abstract: The lipocalin apolipoprotein D (Apo D) is upregulated in peripheral nerves following injury and in regions of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, during aging and progression of certain neurological diseases. In contrast, few studies have examined Apo D expression in the brainstem, a region necessary for survival and generally less prone to age-related degeneration. We measured Apo D expression in whole human brainstem lysates by slot-blot and at higher spatial resolution by quantitative immunohistochemistry in eleven brainstem nuclei (the 4 nuclei of the vestibular nuclear complex, inferior olive, hypoglossal nucleus, oculomotor nucleus, facial motor nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and Roller`s nucleus). In contrast to cortex, hippocampus, and cerebellum, apolipoprotein D was highly expressed in brainstem tissue from subjects (N = 26, 32-96 years of age) with no history of neurological disease, and expression showed little variation with age. Expression was significantly stronger in somatomotor nuclei (hypoglossal, oculomotor, facial) than visceromotor or sensory nuclei. Both neurons and glia expressed Apo D, particularly neurons with larger somata and glia in the periphery of these brainstem centers. Immunostaining was strongest in the neuronal perinuclear region and absent in the nucleus. We propose that strong brainstem expression of Apo D throughout adult life contributes to resistance against neurodegenerative disease and age-related degeneration, possibly by preventing oxidative stress and ensuing lipid peroxidation.
authors.affiliation: Instituto de Neurociencias del Principado de Asturias (INEUROPA), Dpto. Morfología y Biología Celular, Facultad de Biología y Medicina, Universidad de Oviedo, Asturias, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Navarro
authors.forename: Elena
authors.initials: E
authors.lastname: Méndez
authors.forename: Celso
authors.initials: C
authors.lastname: Diaz
authors.forename: Eva
authors.initials: E
authors.lastname: del Valle
authors.forename: Eva
authors.initials: E
authors.lastname: Martínez-Pinilla
authors.forename: Cristina
authors.initials: C
authors.lastname: Ordóñez
authors.forename: Jorge
authors.initials: J
authors.lastname: Tolivia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D053399:Apolipoproteins D / Q000096:biosynthesis*; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies
chemical_list: C024328:APOD protein, human; D053399:Apolipoproteins D; D009419:Nerve Tissue Proteins