title: The glial cell response to a viral vector in the aged brain.
abstract: The normal aged brain undergoes pro-inflammatory changes. We investigated the effect of injecting a potential inflammatory stimulus, an adenoviral vector, on the response of microglia and astroglia in the aged brain. Groups of young (4 months) and old (31 months) male C57BL/Icrfat mice received a unilateral injection into the striatum of adenoviral vector encoding the LacZ gene. After 48 h, the mice were killed and the brains analysed for numbers of activated microglia and macrophages using the biotinylated lectin Griffonia simplicifolia as a marker; astroglia were identified by immunohistochemistry for glial fibrillary acidic protein (GFAP). The cell counts were analysed using two-way analysis of variance (anova). Transgene expression was assessed by beta-galactosidase histochemistry. The numbers of activated microglia in the striatum increased in response to the adenovirus in both young [contralateral 19.5 (3.7), ipsilateral 36 (3.0)] and old [contralateral 23.1 (9.6), ipsilateral 40.8 (6.9)] mice (two-way anova; P < 0.0001), but there was no significant difference between the two age groups. There was a significant age-related increase in the number of GFAP-positive astroglia in the uninjected, contralateral striatum [4 months, 2.5 (1.4); 31 months, 29.7 (9.3)] (two-way anova; P < 0.0001). However, there was no difference in response to the adenovirus in both young [contralateral 2.5 (1.4), ipsilateral 3.2 (1.2)] and old [contralateral 29.7 (9.3), ipsilateral 28.9 (8.2)] mice. We conclude that even though it has been argued that the aged brain is in a pro-inflammatory state, under the experimental conditions used in this study, there was no difference in the nature of the immune response between young and old mice of this strain to an adenoviral load.
authors.affiliation: University of Manchester, School of Medicine, Laboratory Medicine Academic Group and University of Manchester, School of Biological Sciences, Manchester, UK. ioan.davies@man.ac.uk
authors.forename: C A
authors.initials: CA
authors.lastname: Davies
authors.forename: H
authors.initials: H
authors.lastname: Gollins
authors.forename: N
authors.initials: N
authors.lastname: Stevens
authors.forename: A P
authors.initials: AP
authors.lastname: Fotheringham
authors.forename: I
authors.initials: I
authors.lastname: Davies
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007839:Functional Laterality; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007763:Lac Operon; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D001616:beta-Galactosidase