Adenosine A2A Receptor Up-Regulation Pre-Dates Deficits of Synaptic Plasticity and of Memory in Mice Exposed to Aβ1–42 to Model Early Alzheimer’s Disease

The intracerebroventricular (icv) injection of amyloid peptides (Aβ) models Alzheimer’s disease (AD) in mice, as typified by the onset within 15 days deficits memory and hippocampal long-term potentiation (LTP) that are prevented blockade adenosine A2A receptors (A2AR). Since A2AR overfunction is sufficient to trigger deficits, we tested if were upregulated synapses before support hypothesis could be a AD. Six eight after Aβ-icv injection, mice displayed no alterations dependent memory; however, they presented an increased excitability synapses, slight increase LTP magnitude Schaffer fiber-CA1 pyramid density synapses. with SCH58261 (50 nM) normalized slices from sacrificed 7–8 injection. Fifteen evident hippocampal-dependent deterioration, reduced CA1 but hyperexcitability sustained synaptic A2AR, which restored magnitude. This shows upregulation precedes deterioration plasticity, supporting