Effects of repeated citalopram treatment on kainic acid-induced neurogenesis in adult mouse hippocampus.
Previous studies have demonstrated that systemic administration of kainic acid (KA) triggers a cascade of neuroplastic changes in the hippocampus. Intensive neurodegeneration accompanied by immune response and enhanced neurogenesis following local or systemic KA administration in rats and mice has been reported. KA-induced enhancement in proliferative activity of neuronal and glial precursors results in the appearance of immature hyperactive neurons which could be regarded as evidence of dysregulated neural plasticity. In this study we attempted to investigate whether administration of selective serotonin reuptake inhibitor (SSRI) citalopram could inhibit KA-induced reactive gliosis and dysregulated neurogenesis in mice. The results of our study demonstrate that repeated administration of citalopram counteracted KA-induced reactive gliosis and reduced aberrant proliferative activity in the dentate gyrus of the mouse brain. We found that the population of BrdU-positive cells expressing markers for young neurons was decreased following repeated citalopram administration compared to KA-treated animals. These results suggest that repeated citalopram administration could prevent activation of aberrant neuroplasticity in the damaged hippocampus.
Jaako
Külli
K
Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia. kulli.jaako@ut.ee
Zharkovsky
Tamara
T
Zharkovsky
Alexander
A
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage*; D005911:Gliosis / Q000188:drug therapy; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
D015283:Citalopram; D007608:Kainic Acid