Abstract
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 (A2AR), the antagonists of A2AR 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 A2AR antagonist (KW-6002) in the BDNF actions upon hippocampal CA1 LTP. The results showed that chronic blockade of A 2AR 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 A2AR blocking conditions.
Original language | English |
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Pages (from-to) | 99-106 |
Number of pages | 8 |
Journal | Neuropharmacology |
Volume | 83 |
DOIs | |
Publication status | Published - Aug 2014 |
Keywords
- Alzheimer's disease
- Istradefylline
- KW-6002
- TrkB
ASJC Scopus subject areas
- Pharmacology
- Cellular and Molecular Neuroscience