Neuropeptide S Displays as a Key Neuromodulator in Olfactory Spatial Memory.

Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway.

Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.

Effect of the Dispersion States of Azone in Hydroalcoholic Gels on Its Transdermal Permeation Enhancement Efficacy.

The objective of this study was to investigate the effect of dispersion states of azone in gels on the transdermal permeation of levamisole hydrochloride (LH). LH hydroalcoholic gels containing azone of different dispersion states were prepared by varying the contents of azone and Tween 80, and the in vitro transdermal permeation of LH across excised rat skin was evaluated. Depending on the content of azone, mixed solvents, and solubilizer used, azone presented as dissolved molecules, solubilized in micelles, and fine or coarse emulsion droplets in gels. Dramatically increased transdermal permeation of LH within the azone contents between 0.25% and 0.75% indicated high transdermal enhancement efficiency of the molecular or micellar azone, and extra azone that existed as oil droplets did not fully exert transdermal penetration enhancement of LH. Although solubilizer (Tween 80) can greatly increase the solubility of azone, only small amount of Tween 80 (0.5%) in the gel significantly increased the steady-state flux of LH. Addition of extra amount of Tween 80 (>0.5%) reduced the amount of azone distributed in the skin, and thus decreased the transdermal drug permeation. The results partly elucidated the versatile effects of the dispersion states of azone on the transdermal permeation of hydrophilic drug from semisolid gels.

Functional annotation of an expressed sequence tag library from Haliotis diversicolor and analysis of its plant-like sequences.

The small abalone, Haliotis diversicolor, is a widely distributed and cultured species in the subtropical coastal area of China. To identify and classify functional genes of this important species, a normalized expressed sequence tag (EST) library, including 7069 high quality ESTs from the total body of H. diversicolor, was analyzed. A total of 4781 unigenes were assembled and 2991 novel abalone genes were identified. The GC content, codon and amino acid usage of the transcriptome were analyzed. For the accurate annotation of the abalone library, different influencing factors were evaluated. The gene ontology (GO) database provided a higher annotation rate (69.6%), and sequences longer than 800bp were easily subjected to a BLAST search. The taxonomy of the BLAST results showed that lancelet and invertebrates are most closely related to abalone. Sixty-seven identified plant-like genes were further examined by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing, only seven of these were real transcripts in abalone. Phylogenic trees were also constructed to illustrate the positions of two Cystatin sequences and one Calmodulin protein sequence identified in abalone. To perform functional classification, three different databases (GO, KEGG and COG) were used and 60 immune or disease-related unigenes were determined. This work has greatly enlarged the known gene pool of H. diversicolor and will have important implications for future molecular and genetic analyses in this organism.