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

• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2019,（4）
• 页码范围: 661-672
• 页数: 12页
• 语种: 英文

摘要

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.