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.
10.1007/s12264-019-00367-8
- Author:
Yang LI
1
;
Jing LIU
1
;
Xu LIU
1
;
Cun-Jin SU
1
;
Qi-Lin ZHANG
1
;
Zhi-Hong WANG
2
;
Lei-Fang CAO
3
;
Xue-Yan GUO
1
;
Ya HUANG
2
;
Weifeng LUO
4
;
Tong LIU
5
Author Information
1. Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
2. Institute of Neuroscience, Soochow University, Suzhou, 215021, China.
3. Department of Neurology, The Affiliated Hospital of Xiangnan College, Chenzhou, Hunan, 423000, China.
4. Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. lwfwxx@126.com.
5. Jiangsu Key Laboratory of Neuropsychiatric Diseases and the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. liutong80@suda.edu.cn.
- Publication Type:Journal Article
- Keywords:
5-HT;
BDNF;
Botulinum neurotoxin;
Depression;
Hippocampus
- From:
Neuroscience Bulletin
2019;35(4):661-672
- CountryChina
- Language:English
-
Abstract:
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 naïve 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.
