PMID- 30900142 OWN - NLM STAT- MEDLINE DCOM- 20200218 LR - 20200801 IS - 1995-8218 (Electronic) IS - 1673-7067 (Print) IS - 1995-8218 (Linking) VI - 35 IP - 4 DP - 2019 Aug TI - Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain. PG - 661-672 LID - 10.1007/s12264-019-00367-8 [doi] AB - The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naive and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression. FAU - Li, Yang AU - Li Y AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Liu, Jing AU - Liu J AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Liu, Xu AU - Liu X AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. AD - Institute of Neuroscience, Soochow University, Suzhou, 215021, China. FAU - Su, Cun-Jin AU - Su CJ AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. AD - Institute of Neuroscience, Soochow University, Suzhou, 215021, China. AD - Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Zhang, Qi-Lin AU - Zhang QL AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Wang, Zhi-Hong AU - Wang ZH AD - Institute of Neuroscience, Soochow University, Suzhou, 215021, China. FAU - Cao, Lei-Fang AU - Cao LF AD - Department of Neurology, The Affiliated Hospital of Xiangnan College, Chenzhou, Hunan, 423000, China. FAU - Guo, Xue-Yan AU - Guo XY AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. FAU - Huang, Ya AU - Huang Y AD - Institute of Neuroscience, Soochow University, Suzhou, 215021, China. FAU - Luo, Weifeng AU - Luo W AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. lwfwxx@126.com. FAU - Liu, Tong AU - Liu T AUID- ORCID: 0000-0001-9152-5264 AD - Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. liutong80@suda.edu.cn. AD - Institute of Neuroscience, Soochow University, Suzhou, 215021, China. liutong80@suda.edu.cn. AD - College of Life Sciences, Yanan University, Yanan, 716000, China. liutong80@suda.edu.cn. LA - eng PT - Journal Article DEP - 20190321 PL - Singapore TA - Neurosci Bull JT - Neuroscience bulletin JID - 101256850 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 333DO1RDJY (Serotonin) RN - EC 3.4.24.69 (Botulinum Toxins, Type A) SB - IM EIN - Neurosci Bull. 2019 Jun 8;:. PMID: 31177385 MH - Amygdala/drug effects/metabolism MH - Animals MH - Antidepressive Agents/*therapeutic use MH - Behavior, Animal MH - Botulinum Toxins, Type A/*pharmacology/*therapeutic use MH - Brain/drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Depression/*drug therapy MH - Hippocampus/drug effects/metabolism MH - Hypothalamus/drug effects/metabolism MH - MAP Kinase Signaling System/drug effects MH - Male MH - Mice MH - Mice, Inbred ICR MH - Models, Animal MH - Prefrontal Cortex/drug effects/metabolism MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - Serotonin/*metabolism MH - Signal Transduction/*drug effects PMC - PMC6616607 OTO - NOTNLM OT - 5-HT OT - BDNF OT - Botulinum neurotoxin OT - Depression OT - Hippocampus COIS- The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2019/03/23 06:00 MHDA- 2020/02/19 06:00 PMCR- 2020/08/01 CRDT- 2019/03/23 06:00 PHST- 2018/08/25 00:00 [received] PHST- 2019/02/25 00:00 [accepted] PHST- 2019/03/23 06:00 [pubmed] PHST- 2020/02/19 06:00 [medline] PHST- 2019/03/23 06:00 [entrez] PHST- 2020/08/01 00:00 [pmc-release] AID - 10.1007/s12264-019-00367-8 [pii] AID - 367 [pii] AID - 10.1007/s12264-019-00367-8 [doi] PST - ppublish SO - Neurosci Bull. 2019 Aug;35(4):661-672. doi: 10.1007/s12264-019-00367-8. Epub 2019 Mar 21.