Brain-derived neurotrophic factor expression is increased in the hippocampus of 5-HT2C receptor knockout mice

✍ Scribed by Rachel A. Hill; Simon S. Murray; Paul G. Halley; Michele D. Binder; Sally J. Martin; Maarten van den Buuse

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 705 KB
• Volume: 21
• Category: Article
• ISSN: 1050-9631
• DOI: 10.1002/hipo.20759

✦ Synopsis

Several studies have suggested a close interaction between serotonin (5-HT) and BDNF; however, little is known of the specific relationship between BDNF and the 5-HT 2C receptor. Therefore, in this study we investigated BDNF expression in 5-HT 2C receptor knockout mice (5-HT 2C KO). We also assessed functional consequences of any changes in BDNF using a behavioral test battery. Western blot analysis demonstrated a significant 2.2-fold increase in the expression of the mature form of BDNF in 5-HT 2C KO mice when compared with wildtype controls (WT) in the hippocampus (P 5 0.008), but not frontal cortex or striatum. No differences in the expression of the pro-BDNF isoform were found, and the ratio of mature/pro BDNF was significantly increased in 5-HT 2C KO (P 5 0.003). BDNF mRNA expression in the hippocampus was not different between the genotypes. Hence, increased mature BDNF levels in 5-HT 2C KO hippocampus are most likely due to increased extracellular cleavage rates of pro-BDNF to its mature form. Protein expression of the BDNF receptor, tropomycin-related receptor B (TrkB), was also unchanged in the hippocampus, frontal cortex and striatum. With repeated training in a 10-day win-shift radial arm maze task, 5-HT 2C KO and WT showed similar decreases of the number of working memory and reference memory errors. In addition, no genotype specific differences were observed for passive or active avoidance learning. 5-HT 2C KO showed modest locomotor hyperactivity but no differences in tests for anxiety, sensorimotor gating, or depressive-like behaviors; however, in the tail suspension test 5-HT 2C KO showed significantly reduced climbing (P < 0.05). In conclusion, loss of 5-HT 2C receptor expression leads to a marked and selective increase in levels of the mature form of BDNF in the hippocampus. Despite this marked increase, 5-HT 2C KO show only subtle behavioral changes. V V