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The neuroprotective effects of fluoxetine on rat hippocampus, after chronic and acute 5‐fluorouracil treatment (1143.6)
Author(s) -
Chambers Annabelle,
Maqbool Ayesha,
Wigmore Peter
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1143.6
Subject(s) - neurogenesis , neuroprotection , hippocampal formation , fluoxetine , medicine , cell growth , antidepressant , hippocampus , pharmacology , cognitive decline , biology , neuroscience , receptor , serotonin , dementia , genetics , disease
5‐Fluorouracil (5FU) an anti cancer therapy, can cause long term cognitive decline. 5FU reduces cell proliferation in hippocampal neurogenesis which is associated with reduced spatial memory in rodents. Prior antidepressant treatment (Fluoxetine (FLX) prevents the behavioural/cellular effects of 5FU. This quantifies neural stem cell (NSC) number and proliferation after drug treatment. Male rats were treated for 19 days with 10mg/kg/day FLX, via drinking water. Rats received 1 (acute) or 5 (chronic) injections of 35mg/kg 5FU or saline i.p., with or without continued FLX dosing. 1 day or 1 week post treatment, Ki67 (proliferation), Sox 2 (NSC’s) positive cells in the sub granular zone were counted. Acute 5FU causes a significant decline in cell proliferation 1 day later while 1 week animals returned to control levels. Pre‐treatment with FLX prevented the decrease caused by 5FU at one day. Chronic 5FU causes prolonged decline in proliferation, also prevented by FLX. Preliminary results indicate that NSC levels are little affected but their proliferative activity is altered. FLX appears to change the proliferative behaviour of NSC under 5FU treatment. NSC location, number and proliferation are influenced by both compound; use of variations in acute/chronic effects aim to deduce specific mechanisms behind FLX’s neuroprotection. Grant Funding Source : Supported by School of Life Sciences, University of Nottingham, and AstraZeneca UK