Adenosine A2A Receptor Agonist PSB-0777 Modulates Synaptic Proteins and AMPA Receptor Expression in a Dose- and Time-Dependent Manner in Rat Primary Cortical Neurons.

Abstract

Regulating synaptic formation and transmission is critical for the physiology and pathology of psychiatric disorders. The adenosine A2A receptor subtype has attracted widespread attention as a key regulator of neuropsychiatric activity, neuroprotection and injury. In this study, we systematically investigated the regulatory effects of a novel A2A receptor agonist, PSB-0777, on the expression of synaptic proteins and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPA receptors) at the cellular level in a time- and dose-dependent manner. After 30 min of high-dose PSB-0777 stimulation, the expression of Synapsin-1 (Syn-1), postsynaptic density protein 95 (PSD95), and AMPA receptors and the number of synapses were rapidly and significantly increased in rat primary cortical neurons compared with the control. Sustained elevation was found in the low and medium-dose groups after 24 h and 3 d of treatment. In contrast, after stimulation with PSB-0777 for 3 consecutive days, the expression of Syn-1 was decreased, and PSD95, AMPA receptors and the number of synapses were no longer increased in the high-dose group. Our study focuses on the detailed and systematic regulation of synaptic proteins and AMPA receptors by an A2A receptor agonist, PSB-0777, which may result in both beneficial and detrimental effects on neurotransmission and neuroprotection and may contribute to the pathophysiology of psychiatric disorders related to A2A receptors. These experimental data may contribute to understanding of the mechanisms for neuroprotective and therapeutic effect of A2A receptor agonists.

• Authors: Shaolei Luo, Yangyang Hou, Yaping Zhang, Tengfei Ma, Wenping Shao, Chunjie Xiao
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 43 Issue 8 Pg. 1159-1171 (Aug 01 2020) ISSN: 1347-5215 [Electronic] Japan
• PMID: 32448843 (Publication Type: Journal Article)

Chemical References

• Disks Large Homolog 4 Protein
• Furans
• Neuroprotective Agents
• PSB-0777
• Receptor, Adenosine A2A
• Receptors, AMPA
• Synapsins

Topics

• Animals
• Cells, Cultured
• Cerebral Cortex (drug effects, metabolism)
• Disks Large Homolog 4 Protein (genetics)
• Dose-Response Relationship, Drug
• Female
• Furans (pharmacology)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Adenosine A2A (physiology)
• Receptors, AMPA (genetics)
• Synapses (drug effects, physiology)
• Synapsins (genetics)
• Synaptic Transmission (drug effects)