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Evidence for the existence of A2AR-TrkB heteroreceptor complexes in the dorsal hippocampus of the rat brain: Potential implications of A2AR and TrkB interplay upon ageing.
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2020-06-18 , DOI: 10.1016/j.mad.2020.111289
Michael Di Palma 1 , Stefano Sartini 2 , Davide Lattanzi 2 , Riccardo Cuppini 2 , Mariana Pita-Rodriguez 3 , Yoslandy Diaz-Carmenate 4 , Manuel Narvaez 4 , Kjell Fuxe 5 , Dasiel O Borroto-Escuela 6 , Patrizia Ambrogini 2
Affiliation  

Adenosine A2A receptors (A2AR) are crucial in facilitating the BDNF action on synaptic transmission in the rat hippocampus primarily upon ageing. Furthermore, it has been suggested that A2AR-Tropomyosin related kinase B receptor (TrkB) crosstalk has a pivotal role in adenosine A2AR-mediated modulation of the BDNF action on hippocampal plasticity. Considering the impact of the above receptors interplay on what concerns BDNF-induced enhancement of synaptic transmission, gaining a better insight into the mechanisms behind this powerful crosstalk becomes of primary interest. Using in situ proximity ligation assay (PLA), the existence of a direct physical interaction between adenosine A2AR and TrkB is demonstrated. The A2AR-TrkB heteroreceptor complexes show a heterogeneous distribution within the rat dorsal hippocampus. High densities of the heteroreceptor complexes were observed in the pyramidal cell layers of CA1-CA3 regions and in the polymorphic layer of the dentate gyrus (DG). The stratum radiatum of the CA1-3 regions showed positive PLA signal in contrast to the oriens region. The molecular and granular layers of the DG also lacked significant densities of PLA positive heteroreceptor complexes, but subgranular zone showed some PLA positive cells. Their allosteric receptor-receptor interactions may significantly modulate BDNF signaling impacting on hippocampal plasticity which is impaired upon ageing.



中文翻译:

大鼠大脑背侧海马中存在 A2AR-Tr​​kB 异源受体复合物的证据:A2AR 和 TrkB 相互作用对衰老的潜在影响。

腺苷 A2A 受体 (A2AR) 在促进 BDNF 对大鼠海马突触传递的作用方面至关重要,主要是在衰老时。此外,有人提出 A2AR-原肌球蛋白相关激酶 B 受体 (TrkB) 串扰在腺苷 A2AR 介导的 BDNF 对海马可塑性的作用的调节中起关键作用。考虑到上述受体相互作用对 BDNF 诱导的突触传递增强的影响,更好地了解这种强大的串扰背后的机制成为主要兴趣。就地使用在邻近连接试验 (PLA) 中,腺苷 A2AR 和 TrkB 之间存在直接的物理相互作用。A2AR-Tr​​kB 异质受体复合物在大鼠背海马内表现出异质性分布。在 CA1-CA3 区域的锥体细胞层和齿状回 (DG) 的多态层中观察到高密度的异受体复合物。与东方地区相比,CA1-3 地区的辐射层显示出正 PLA 信号。DG 的分子层和颗粒层也缺乏 PLA 阳性异受体复合物的显着密度,但颗粒下区域显示一些 PLA 阳性细胞。它们的变构受体-受体相互作用可能会显着调节 BDNF 信号,影响海马可塑性,而海马可塑性会随着年龄的增长而受损。

更新日期:2020-06-23
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