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首页> 外文期刊>Neuropharmacology >Impact of in vivo chronic blockade of adenosine A_(2A) receptors on the BDNF-mediated facilitation of LTP
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Impact of in vivo chronic blockade of adenosine A_(2A) receptors on the BDNF-mediated facilitation of LTP

机译:体内慢性阻断腺苷A_(2A)受体对BDNF介导的LTP促进的影响

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摘要

Brain-derived neurotrophic factor (BDNF) through the activation of its receptor (TrkB-FL) exert well-described neuroprotective effects playing a major role in hippocampal synaptic transmission and plasticity such as long-term potentiation (LTP), a molecular surrogate for learning and memory. Impairments in BDNF signalling have been associated to several neurodegenerative disorders such as Alzheimer's disease (AD). Therefore, the reestablishment of BDNF actions is considered a promising strategy for AD treatment. While, most of BDNF synaptic actions, namely on LTP, require the activation of adenosine A_(2A) receptor (A_(2A)R), the antagonists of A_(2A)R have been proven to prevent AD induced deficits in different animal models. Therefore in this work we aimed to evaluate the impact of a chronic in vivo oral administration of an A_(2A)R antagonist (KW-6002) in the BDNF actions upon hippocampal CAT LTP.The results showed that chronic blockade of A_(2A)R in male Wistar rats inhibits the facilitatory action of BDNF upon LTP on hippocampal CA1 area and decreases both mRNA and protein levels of the TrkB-FL receptor in hippocampus. These findings imply that BDNF signalling may be affected in chronic A_(2A)R blocking conditions.
机译:脑源性神经营养因子(BDNF)通过其受体(TrkB-FL)的激活发挥了良好描述的神经保护作用,在海马突触传递和可塑性中起着重要作用,例如长期增强(LTP)(一种学习的分子替代物)和记忆。 BDNF信号传导障碍已与多种神经退行性疾病(例如阿尔茨海默氏病(AD))相关。因此,BDNF动作的重建被认为是有前途的AD治疗策略。尽管大多数BDNF突触作用(即对LTP的作用)都需要激活腺苷A_(2A)受体(A_(2A)R),但已证明A_(2A)R的拮抗剂可预防AD诱导的不同动物模型的缺陷。因此,在这项工作中,我们旨在评估长期口服A_(2A)R拮抗剂(KW-6002)对BDNF对海马CAT LTP的影响。结果表明,慢性阻断A_(2A)雄性Wistar大鼠中的R抑制LTP对海马CA1区域的BDNF的促进作用,并降低海马TrkB-FL受体的mRNA和蛋白水平。这些发现暗示在慢性A_(2A)R阻断条件下BDNF信号传导可能受到影响。

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