A 1-adenosine receptor gene expression in fetal rat brain

Abstract

Adenosine influences neurotransmitter release, neuronal excitability, and firing rate, through A 1-adenosine receptors (A 1-R). Caffeine and related methylxanthines are adenosine receptor antagonists. Exposure of developing rodents to caffeine is associated with subtle, long-term changes in neurochemistry and behavior. The developmental appearance of A 1-R gene expression was examined in rats by in situ hybridization. On gestational day (GD) 10, A 1-R mRNA was expressed at very high levels in placental mesometrium. Expression of A 1-R mRNA in brain was first detected on GD 14. Hybridization was restricted to portions of neuroepithelium, caudate-putamen, piriform cortex, hypoglossal nucleus, and ventral horn of spinal cord. Neuroepithelial A 1-R mRNA increased in intensity and distribution at subsequent ages, reaching a maximum on GD 20 (the latest age studied). Hybridization signal was detected, with regional variation in intensity, throughout much of the brain by GD 16, with additional increases in extent and intensity through GD 20. Generally, a caudal ⪢ rostral gradient of hybridization intensity was apparent. The distribution on GD 20 resembled the widespread yet heterogeneous pattern observed in the adult, with high levels of A 1-R gene expression in cortex, hippocampus, thalamus, cerebellum, pontine nuclei, brainstem motor nuclei, and spinal cord. Northern blot analysis confirmed the age-related increase in abundance of A 1-R transcripts (ca. 3.5 and 5.5 kb). The early and widespread expression of A 1-R mRNA, coupled with previous reports of prenatal A 1-R binding, suggests that adenosine and adenosine antagonists, including caffeine, may influence neuronal differentiation, migration or synaptogenesis, thus producing long-lasting effects on brain and behavior.