Immunohistochemical localization and quantification of glial fibrillary acidic protein and synaptosomal-associated protein (mol. wt 25000) in the ageing hippocampus following administration of 5,7-dihydroxytryptamine.
Responses to injury in the ageing hippocampus were assessed utilizing the synaptic markers glial fibrillary acidic protein and synaptosomal-associated protein (mol. wt 25,000) following administration of the neurotoxin, 5,7-dihydroxytryptamine, into the fimbria-fornix and cingulum bundle to denervate serotonergic afferent input to the dorsal hippocampus. Age-dependent alterations in hippocampal immunohistochemical localization of glial fibrillary acidic protein and synaptosomal-associated protein were evaluated in female Fischer 344 rats following serotonergic deafferentation with 5,7-dihydroxytryptamine. Across the lifespan, as indicated by measurements taken at three, 18, 21 and 29 months, marked increases in glial fibrillary acidic protein, but not synaptosomal-associated protein immunoreactivity, occurred throughout the hippocampus at 21 and 29 months compared to three and 18 months. Following three weeks pretreatment with 5,7-dihydroxytryptamine (20 microg total dose) or vehicle (0.1% ascorbic saline; 2 microl total volume) infused in the fimbria-fornix/cingulum bundle, immunohistochemical analysis demonstrated marked increases of glial fibrillary acidic protein, but not synaptosomal-associated protein, in the 18-month 5,7-dihydroxytryptamine group compared to the 18-month vehicle and 3-month 5,7-dihydroxytryptamine groups. Additionally, a significant increase in glial fibrillary acidic protein concentration was found by enzyme-linked immunosorbent assay in the 18-month 5,7-dihydroxytryptamine group compared to the 18-month vehicle and three-month 5,7-dihydroxytryptamine groups. These results demonstrate that selective neurotoxicant damage of the hippocampal serotonergic system differentially alters the expression of glial fibrillary acidic protein. This approach may provide a valuable tool to determine the ability of the hippocampus to respond to age-related neurodegenerative injury.
J.M. Lakoski Centers for Disease Control and Prevention, NIOSH, Health Effects Laboratory Division TMBB (MS 3014), 1095 Willowdale Road, Morgantown, WV 26505-2888, USA