Role of BDNF in basolateral amygdala-prelimbic cortex in perioperative neurocognitive disorders and relationship with TrkB receptors in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of basolateral amygdala (BLA)-prelimbic cortex (PL) brain-derived neurotrophic factor (BDNF) in perioperative neurocognitive disorders (PND) and its relationship with tyrosine kinase B (TrkB) receptors in mice.Methods:Forty-eight clean-grade healthy C57BL/6J mice, aged 6 months, weighing 25-30 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), surgery group (group S), BDNF overexpression in BLA group (group B) and BDNF overexpression in BLA+ ANA-12 injection in PL group (group A). In group S, at 30 min after the end of training session of fear conditioning system, exploratory laparotomy was performed.In group B, recombinant adenovirus 0.3 μl was injected in BLA, fear conditioning test was performed 3 weeks later, and exploratory laparotomy was performed at 30 min after the end of the training session of fear conditioning system.In group A, recombinant adenovirus 0.3 μl was injected in BLA, catheterization was performed in PL, the fear conditioning test used performed 3 weeks later, TrkB receptor antagonist ANA-12 0.25 μg was given in PL starting from 30 min before training session, and exploratory laparotomy was performed at 30 min after training session.Test session was started at 24 h after the end of training session of fear conditioning system, and the percentage of time spent freezing was calculated in all groups.At 30 min after the end of the behavioral test, the expression of BDNF in brain areas, phosphorylated TrkB (p-TrkB) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERKl/2) was determined by Western blot, and the expression BDNF mRNA in BLA was detected using reverse transcription fluorescence quantitative polymerase chain reaction assay. Results:Compared with group C, the percentage of time spent freezing was significantly decreased, and expression of BNDF protein and its mRNA in BLA and BDNF, p-TrkB and p-ERK1/2 in PL was down-regulated in group S ( P<0.05). Compared with group S, the percentage of time spent freezing was significantly increased, and expression of BNDF protein and its mRNA in BLA and BDNF, p-TrkB and p-ERK1/2 in PL was up-regulated in group B ( P<0.05). Compared with group B, the percentage of time spent freezing was significantly decreased, and expression of p-TrkB and p-ERK1/2 in PL was down-regulated in group A ( P<0.05). Conclusion:The mechanism of PND is probably related to reduction of BDNF secretion from BLA to PL caused by down-regulation of BDNF expression in BLA, and decreasing of post-synaptic phosphorylation of TrkB receptors in mice.