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. (September 2020)

• Record Type: Journal Article
• Authors: Di Palma, Michael; Sartini, Stefano; Lattanzi, Davide; Cuppini, Riccardo; Pita-Rodriguez, Mariana; Diaz-Carmenate, Yoslandy; Narvaez, Manuel; Fuxe, Kjell; Borroto-Escuela, Dasiel O.; Ambrogini, Patrizia
• Is Part Of: Mechanisms of ageing and development. Volume 190(2020)
• Publication Date: 2020-09
• Subjects: Heteroreceptor complexes -- Hippocampus -- In situ proximity ligation assay -- Adenosine receptor -- Tropomyosin-related kinase B receptor; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2020.111289
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: Several GPCRs can directly interact with receptor tyrosine kinases (RTKs). Adenosine A2A receptors are crucial in modulating BDNF action in the hippocampus. A direct interaction A2AR-Tropomyosin related kinase B receptor (TrkB) is suggested. In situ PLA revealed the existence of A2AR-TrkB complexes in rat hippocampus. This A2AR-TrkB physical interaction may have an impact upon ageing. Abstract: 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.