Brain-derived neurotrophic factor expression is increased in the hippocampus of 5-HT(2C) receptor knockout mice.
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 wild-type controls (WT) in the hippocampus (P = 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 = 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.
Hill
Rachel A
RA
Behavioral Neuroscience Laboratory, Mental Health Research Institute, Parkville, Victoria, Australia 3052. r.hill@mhri.edu.au
Murray
Simon S
SS
Halley
Paul G
PG
Binder
Michele D
MD
Martin
Sally J
SJ
van den Buuse
Maarten
M
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003863:Depression / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; D044405:Receptor, Serotonin, 5-HT2C; C426674:brain-derived neurotrophic factor precursor; D012701:Serotonin; D020813:Receptor, trkB