Early Life Stress Alters Gene Expression and Cytoarchitecture in the Prefrontal Cortex Leading to Social Impairment and Increased Anxiety.

Early life stress (ELS), such as abuse, neglect, and maltreatment, exhibits a strong impact on the brain and mental development of children. However, it is not fully understood how ELS affects social behaviors and social-associated behaviors as well as developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice until adolescence and investigated these behaviors and PFC characteristics in adolescent mice. We found the ELS induced social impairments in social novelty, social interaction, and social preference in adolescent mice. We also observed increases of anxiety-like behaviors in ELS mice. In histological analysis, we found a reduced number of neurons and an increased number of microglia in the PFC of ELS mice. To identify the gene associated with behavioral and histological features, we analyzed transcriptome in the PFC of ELS mice and identified 15 differentially expressed genes involved in transcriptional regulation, stress, and synaptic signaling. Our study demonstrates that ELS influences social behaviors, anxiety-like behaviors through cytoarchitectural and transcriptomic alterations in the PFC of adolescent mice.

Rapid optical tissue clearing using poly(acrylamide-co-styrenesulfonate) hydrogels for three-dimensional imaging.

Optical tissue clearing methods are attractive for three-dimensional imaging of intact tissues and organs. A CLARITY (clear lipid-exchanged acrylamide-hybridized rigid imaging/immunostaining/in situ-hybridization-compatible tissue-hydrogel) method using polyacrylamide gels was recently developed. In the current study, we used poly(acrylamide-co-styrenesulfonate) gels as a polyelectrolyte gel for a passive CLARITY method. First, radical copolymerization of acrylamide (AAm) and sodium p-styrenesulfonate (SS) at different ratios was performed. The composition of the copolymer could be controlled by changing the monomer ratio. With increased SS content, the molecular weight decreased and the refractive index slightly increased. The poly(AAm-co-SS) hydrogels with a higher SS content were more swollen and looser. The clearing time could be reduced using the poly(AAm-co-SS) hydrogel with a higher SS content. Three-dimensional fluorescence imaging of the poly(AAm-co-SS) hydrogel-cleared tissues was successfully performed after treatment using a blue fluorescent DNA stain. Therefore, the use of the poly(AAm-co-SS) hydrogel improved the clearing process in the passive CLARITY method, and the technique is useful for fluorescence imaging of DNA. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2297-2304, 2019.

Effect of alkyl group on transnitrosation of N-nitrosothiazolidine thiocarboxamides.

S-Nitrosoglutathione (GSNO) relaxes vascular smooth muscles, prevents platelet aggregation, and acts as a potential in vivo nitric oxide donor. 3-Nitroso-1,3-thiazolidine-4-thiocarboxamide (1), a N-nitrosothio-proline analogue, exhibited a high GSNO formation activity. In this study, two compounds (2 and 3) based on compound 1 were newly synthesized by introducing either one or two methyl groups onto a nitrogen atom on the thioamide substituent in 1. The pseudo-first-order rate constants (kobs) for the GSNO formation for the reaction between the compound and glutathione followed the order 1>2≒3. Thus, the introduction of a methyl group(s) onto the thioamide group led to a decrease in the transnitrosation activity. On the basis of density functional theoretical calculations, the transnitrosation for the N-nitrosothiazolidine thiocarboxamides was proposed to proceed via a bridged intermediate pathway. Specifically, the protonated compound 1 forms a bridged structure between the nitrogen atom in the nitroso group and two sulfur atoms-one in the ring and the other in the substituent. The bridged intermediate gives rise to a second intermediate in which the nitroso group is bonded to the sulfur atom in the thioamide group. Finally, the nitroso group is transferred to GSH to form GSNO.

Transnitrosation of alicyclic N-nitrosamines containing a sulfur atom.

Aromatic and aliphatic nitrosamines are known to transfer a nitrosonium ion to another amine. The transnitrosation of alicyclic N-nitroso compounds generates S-nitrosothiols, which are potential nitric oxide donors in vivo. In this study, certain alicyclic N-nitroso compounds based on non-mutagenic N-nitrosoproline or N-nitrosothioproline were synthesised, and the formation of S-nitrosoglutathione (GSNO) was quantified under acidic conditions. We then investigated the effect of a sulfur atom as the substituent and as a ring component on the GSNO formation. In the presence of thiourea under acidic conditions, GSNO was formed from N-nitrosoproline and glutathione, and an N-nitroso compound containing a sulfur atom and glutathione produced GSNO without thiourea. The quantity of GSNO derived from the reaction of the N-nitrosamines containing a sulfur atom and glutathione was higher than that from the N-nitrosoproline and glutathione plus thiourea. Among the analogues that contained a sulfur atom either in the ring or as a substituent, the thiazolidines produced a slightly higher quantity of GSNO than the analogue with a thioamide group. A compound containing sulfur atoms both in the ring and as a substituent exhibited the highest activity for GSNO formation among the alicyclic N-nitrosamines tested. The results indicate that the intramolecular sulfur atom plays an important role in the transnitrosation via alicyclic N-nitroso compounds to form GSNO.

Direct formation of a 2D redox-active adlayer based on a bisterpyridine derivative and Co2+ on a Au(111) electrode.

The direct assembly of single component 4',4''''-(1,4-phenylene)bis(2,2' : 6',2''-terpyridine) (PTPy) and Co(2+) and PTPy mixed arrays was examined on a Au(111) surface by a simple immersion method. A redox active 2D adlayer consisting of a bisterpyridine derivative and cobalt ions was found to form directly on Au(111) from solution, suggesting that new nanostructures and/or adlayers with electrochemical activity can be precisely designed and controlled by selection of the metal ion and ligand.