Apolipoprotein D Expression in Human Brain Reactive Astrocytes

Departamento de Morfología y Biología Celular, Facultad de Biología y Medicina, Universidad de Oviedo, España.
Journal of Histochemistry and Cytochemistry (Impact Factor: 1.96). 11/2003; 51(10):1285-90. DOI: 10.1177/002215540305101005
Source: PubMed


Astrocytosis is a hallmark of damage that frequently occurs during aging in human brain. Astrocytes proliferate in elderly subjects, becoming hypertrophic and highly immunoreactive for glial fibrillary acidic protein (GFAP). These cells are one type that actively responds in the repair and reorganization of damage to the neural parenchyma and are a source of several peptides and growth factors. One of these biomolecules is apolipoprotein D (apo D), a member of the lipocalin family implicated in the transport of small hydrophobic molecules. Although the role of apo D is unknown, increments in brain apo D expression have been observed in association with aging and with some types of neuropathology. We have found an overexpression of apo D mRNA in reactive astrocytes by in situ hybridization in combination with immunohistochemistry for apo D in normal aged human brains. The number of double-labeled cells varied according to the cerebral area and the gliosis grade. The possible significance of this increased synthesis of apo D in reactive astrocytes is discussed in relation to the role of apo D in aging and in glial function.

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    • "All human brain tissue samples were provided by the Department of Pathologic Anatomy of the Central Hospital of Asturias and obtained from necropsies within 6 h of death. These samples were the same as those used in previous studies by our group [8-10,21]. Twenty-six brainstems from men 32−92 years old were examined. None of the patients presented a previous inner ear or neurological disease. "
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    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.
    PLoS ONE 09/2013; 8(10):e77852. DOI:10.1371/journal.pone.0077852 · 3.23 Impact Factor
    • "In this way, it has been reported that steroids, such as androgens , estrogens, and glucocorticoids, are very important in the regulation of apo D expression, suggesting that its expression could be directly or indirectly modulated by changes in cellular proliferation [5] [6] [7] [8] [9] [10]. Furthermore, apo D expression is linked to cellular aging in nervous tissue; apo D is abundant in glial cells of aged individuals and in patients with neuronal cell aging disorders [11] [12]. In normal human fibroblast cell lines, apo D is secreted when cells have reached a senescent stage [10]. "
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