Cellular studies of neurodegeneration in the serotonergic system of the aging rat hippocampus.

摘要

The serotonin (5-hydroxytryptatnine; 5-HT) system of the hippocampus has a role in normal cognitive function and age-dependent neurodegenerative disorders. The current experiments test the hypothesis that the hippocampus differentially responds to selective serotonergic insult in young and old animals.; Alterations hippocampal CA3 subfield pyramidal neuronal function were evaluated in female Fischer 344 rats (2 and 17 mo) following bilateral administration of the neurotoxicant 5,7-dihydroxytryptamine (5,7-DHT) in the fimbria-fornix/cingulum bundle (FF/CB). The time to recovery of cell firing following 5-HT application was significantly increased in the 18 mo 5,7-DHT group compared age- and treatment-matched groups suggesting alterations in presynaptic function, specifically the serotonin transporter (5-HTT). Responses to injury in the aging hippocampus were assessed utilizing glial fibrillary acidic protein and demonstrated a significant increase of GFAP expression and levels in the 18 mo 5,7-DHT group compared to age- and treatment-matched groups.; The hippocampal 5-HTT was examined and loss of 5-HTT immunoreactivity was observed in both age groups at 7 days post-lesion, with recovery in only young animals at 21 days. Quantitative autoradiography demonstrated a significant recovery of 5-HTT binding sites in young, but not old animals at 21 days post-lesion. Hippocampal CAI pyramidal neuronal function showed the time to recovery of cell firing following 5-HT application significantly increased in the 18 mo 5,7-DHT group compared to age- and treatment-matched groups at 21 days. Retrograde tracing experiments demonstrated a marked decline in MRN cell density at 7 days post-lesion, with partial recovery of neuronal density in only young animals at 21 days post-lesion.; The present findings indicate that age-related declines in 5-HTT function and expression occur shortly following injury to the hippocampal serotonergic system, with recovery in young, but not old animals, and the disrupted axonal transport in older animals may help explain these changes. Thus, this animal model may provide a basis for systematic studies on neurotrophic or pharmacologic intervention of degenerative processes, as well as neuroprotective and regenerative mechanisms following selective hippocampal serotonergic.