Translational patterns of ionotropic glutamate and GABA receptors during brain development and behavioral stimuli revealed by polysome profiling.

mRNA translation is critical for regulation of various aspects of the nervous system. Ionotropic glutamate and gamma-aminobutyric acid type A (GABAA ) receptors are fundamental synaptic ion channels that control excitatory and inhibitory synaptic transmission, respectively. However, little is known about the translation of these receptors during brain development and function. By utilizing polysome profiling, a powerful tool for investigating translational machinery and mRNA translational states, we characterized the translational patterns of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), and GABAA receptor subunits, and compared them with total mRNA and protein levels during mouse brain development, in different brain regions, and in response to behavioral stimuli. Most of the receptor subunits exhibited developmental changes at total mRNA, translation, and protein levels, among which translation of Gria1, Gria2, Grin1, Grin2a, Gabra1, and Gabrg2 contributed greatly to their protein levels. Most of the receptor subunits also displayed differentiated levels of total mRNA, translation, and protein in the prefrontal cortex and hippocampus, among which translation of Gria1, Gria2, Gabrb2, and Gabrg2 contributed to their protein levels. Finally, we showed that acute foot shock stress had a rapid influence in both the prefrontal cortex and hippocampus, with the prefrontal cortex displaying more changes at translational and protein levels. Notably, Grin2a is translationally repressed by stress which was followed by a decrease of GluN2A protein in both brain regions. Together, this study provides a new understanding of the translational patterns of critical ionotropic synaptic receptors during brain development and behavioral stress.

Anti-inflammatory naphthoquinone-monoterpene adducts and neolignans from Eugenia caryophyllata.

A phytochemical investigation on the buds of edible medicinal plant, Eugenia carvophyllata, led to the discovery of seven new compounds, caryophones A-G (1-7), along with two biogenetically-related known ones, 2-methoxy-7-methyl-1,4-naphthalenedione (8) and eugenol (9). Compounds 1-3 represent the first examples of C-5-C-1' connected naphthoquinone-monoterpene adducts with a new carbon skeleton. Compounds 4-7 are a class of novel neolignans with unusual linkage patterns, in which the C-9 position of one phenylpropene unit coupled with the aromatic core of another phenylpropene unit. The chemical structures of the new compounds were determined based on extensive spectroscopic analysis, X-ray diffraction crystallography, and quantum-chemical calculation. Among the isolates, compounds (-)-2, 3, 6, and 9 showed significant in vitro inhibitory activities against respiratory syncytial virus (RSV)-induced nitric oxide (NO) production in RAW264.7 cells.