阻断内侧前额叶皮质TrkB受体对大鼠认知和海马BDNF表达的影响

The effects of Trk B inhibition in the m PFC on cognitive function and BDNF expression in the hippocampus of rats

脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)广泛参与了个体学习和记忆等认知功能,通过与其酪氨酸激酶受体(tyrosine kinase,TrkB)特异性结合,实现其多种神经生化功能。本研究观察了TrkB受体阻断剂ANA-12的慢性内侧前额叶皮质(medial prefrontal cortex,mPFC)注射对大鼠旷场行为、Morris水迷宫空间学习和逆反学习的影响。研究结果表明,mPFC的慢性BDNF阻断显著降低了大鼠在逆反学习测试中的逃离潜伏期和运动距离即增强了大鼠的逆反学习能力,但不影响其旷场行为和水迷宫空间学习能力。同时,慢性阻断mPFC-TrkB受体也并未导致大鼠海马BDNF蛋白含量的显著改变。这些结果提示,对于大鼠的Morris水迷宫空间学习和逆反学习,mPFC-BDNF主要在逆反学习调节中发挥重要作用。这对于进一步探索海马和mPFC在调节个体认知功能中各自的作用及其潜在的相互关系提供了有力的证据和支持。

Brain derived neurotrophic factor（BDNF） is a member of the neurotrophin family of growth factors and is critically involved in many cognitive functions such as learning and memory. TrkB, the specific receptor of BDNF, can bind with its ligand and regulate various neural-biochemical functions. The hippocampus and medial prefrontal cortex（mPFC） are crucial brain areas involved in regulating memory and learning; BDNF in the hippocampus and mPFC plays an important role in these cognitive functions. Previous studies have focused on the effects of BDNF in the hippocampus and mPFC on cognitive function, however details of the interaction and co-regulation between these two areas are still unclear.In this study, male rats were obtained on postnatal day（PND） 35 and cannulas were implanted bilaterally in mPFC. One week post surgery, rats were given chronic bilateral micro-injections of ANA-12, a specific TrkB receptor antagonist, into the mPFC for seven days. Then, rats＇ behaviors in the open field test, and spatial learning and reversal learning in the Morris water maze（MWM） were observed through early adulthood（PND 56）. After the behavioral tests, rats were sacrificed and samples of hippocampal tissue were obtained for BDNF measurement using the western blot technique.The results of the present study show that chronic blocking of TrkB in the mPFC significantly reduces the escape latency and distance traveled in the reversal learning stage of the MWM, suggesting enhanced reversal learning in early adult rats. The distance traveled and time spent in the central area of the open field, as well as the escape latency and distance traveled in the spatial learning stage of the MWM were not affected by blocking TrkB in the mPFC. The results of the western blot show that the expression of BDNF in the hippocampus was not affected by blocking mPFC TrkB. These results suggest that BDNF in the mPFC plays an important role in regulating reversal learning in young adult rats, but the influence of mPFC-BDNF on the spatial learning of rats is relatively limited. In addition, the expression of BDNF in the hippocampus seems to not be directly regulated by chronic blocking of BDNF in the mPFC.The results of the present study demonstrate that inhibition of TrkB in the mPFC improves early adult rats＇ reversal learning in the MWM without changing the spatial learning, nor does this specific blokade affect BDNF expression in the hippocampus. These results underscore the need for further exploration of the role of the hippocampus and mPFC in regulating cognitive functions such as learning and memory, and the relationships between these two important brain areas. Furthermore, the results provide a tentative theoretical basis for studying changes in cognitive function related to mental disease and the underlying neurobiological mechanisms.