Reproductive role of miRNA in the hypothalamic-pituitary axis.

The hypothalamic-pituitary-gonadal (HPG) axis plays a critical role in regulating reproductive function. Gonadotropin-releasing hormone (GnRH), which is secreted by the hypothalamus, acts on pituitary gonadotrophs to stimulate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and secretion, ultimately affecting the animal's fertility. MicroRNAs are small, non-coding RNAs that are widely expressed throughout the brain and can fine-tune gene expression post-transcriptionally. Recently, growing evidence has unveiled the central position of miRNAs within a key regulatory process involving GnRH secretion and subsequent activation in the pituitary. Although transcriptional regulation of reproduction has been well studied, the post-transcriptional processes are less well understood. In this review, we elaborate comprehensively on the critical role of miRNAs in the reproductive process, including both temporal and spatial aspects. A better understanding of how miRNAs impact the neuroendocrine system may improve our knowledge of reproduction and provide novel targets for therapeutic development.

The Inhibitory Effects of RFamide-Related Peptide 3 on Luteinizing Hormone Release Involves an Estradiol-Dependent Manner in Prepubertal but Not in Adult Female Mice.

The mammalian gonadotropin-inhibitory hormone (GnIH) ortholog, RFamide-related peptide (RFRP), is considered to act on gonadotropin-releasing hormone (GnRH) neurons and the pituitary to inhibit gonadotropin synthesis and release. However, there is little evidence documenting whether RFamide-related peptide 3 (RFRP-3) plays a primary role in inhibition of the hypothalamo-pituitary-gonadal (HPG) axis prior to the onset of puberty. The present study aimed to understand the functional significance of the neuropeptide on pubertal development. The developmental changes in reproductive-related gene expression at the mRNA level were investigated in the hypothalamus of female mice. The results indicated that RFRP-3 may be an endogenous inhibitory factor for the activation of the HPG axis prior to the onset of puberty. In addition, centrally administered RFRP-3 significantly suppressed plasma luteinizing hormone (LH) levels in prepubertal female mice. Surprisingly, centrally administered RFRP-3 had no effects on plasma LH levels in ovariectomized (OVX) prepubescent female mice. In contrast, RFRP-3 also inhibited plasma LH levels in OVX prepubescent female mice that were treated with 17beta-estradiol replacement. Our study also examined the effects of RFRP-3 on plasma LH release in adult female mice that were ovariectomized at dioestrus, with or without estradiol (E2). Our results showed that the inhibitory effects of RFRP-3 were independent of E2 status. Quantitative real-time PCR and immunohistochemistry analyses showed that RFRP-3 inhibited GnRH expression at both the mRNA and protein levels in the hypothalamus. These data demonstrated that RFRP-3 could effectively suppress pituitary LH release, via the inhibition of GnRH transcription and translation in prepubescent female mice, which is associated with estrogen signaling pathway and developmental stages.

Comparative analysis of gene expression profiles between cortex and thalamus in Chinese fatal familial insomnia patients.

Fatal familial insomnia (FFI) is a special subtype of genetic human prion diseases that is caused by the D178N mutation of the prion protein gene (PRNP). According to the surveillance data from 2006, FFI accounts for about half of all genetic prion disease cases in China. In this study, global expression patterns of the thalamus and parietal cortex from three patients with FFI were analyzed by Affymetrix Human Genome U133+ 2.0 chip. A total of 1,314 genes in the thalamus and 332 ones in the parietal lobe were determined to be differentially expressed genes (DEGs). The percentage of upregulated DEGs is much less in the thalamus (19.3 %) than that in the parietal lobe (42.8 %). Moreover, 255 of those DEGs showed the same altering tendencies in both tested regions, including 99 upregulated and 156 downregulated ones. The reliability of the results was confirmed by the real-time RT-PCR assays. There were 1,152 and 531 biological processes affected in the thalamus and the parietal lobe, respectively, as well as 391 overlapping ones in both regions. The most significantly changed molecular functions included transcription and DNA-dependent regulation of transcription, RNA splicing, mitochondrial electron transport, etc. The changed functions in the thalamus contained more numbers of DEGs than parietal lobe. According to KEGG classification, there were 167 and 115 different pathways changed in the thalamus and the parietal lobe, respectively, while 102 were changed in both. Interestingly, the top three changed pathways in the three groups mentioned above were Parkinson's disease, Alzheimer's disease, and oxidative phosphorylation. These results demonstrate the greater damage in the thalamus than in the parietal lobe during FFI pathogenesis, which is consistent with previous pathological observations. This study aims to describe the global expression profiles in various brain regions of FFI while proposing useful clues for understanding the pathogenesis of FFI and selecting potential biomarkers for diagnostic and therapeutic tools.

Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia.

Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by rapidly progressive insomnia, prominent autonomic alterations and behavioral disturbance. The D178N mutation of the prion protein gene (PRNP) on chromosome 20 in conjunction with methionine at codon 129 is a molecular feature. Although the neuropathological characteristics of FFI are well documented, the neuropathologic and pathogenic features of FFI patients remain poorly understood. Six brain regions of postmortem brains from 3 FFI patients were examined using immunohistochemistry, western blot analyses and quantitative real-time PCR. In all 3 brain specimens, reactive astrogliosis was found to be more severe in the thalamus than in the cortex regions. Western blot analyses showed that all three brains expressed PrP, but only 2 were associated with significantly weak proteinase K (PK) resistance. However, the conformational stabilities of PrPSc in the 3 FFI brains were significantly weaker than those presented in a G114V genetic Creutzfeldt-Jakob disease (gCJD) case. Immunohistochemistry and western blot analyses showed comparable amounts of neuron-specific enolase (NSE)-positive stained cells and NSE protein among the different regions in the three brains. In addition, the transcriptional levels of glial fibrillary acidic protein (GFAP) and NSE-specific mRNAs were coincident with the expression of these proteins. In conclusion, in the present study, we described the detailed regional neuropathology of FFI cases.

Efficient and quick inactivation of SARS coronavirus and other microbes exposed to the surfaces of some metal catalysts.

OBJECTIVE: To study the two metal catalysts Ag/Al2O3 and Cu/Al2O3 that interdict the transmission pathway for SARS and other respiratory infectious diseases. METHODS: Two metal catalysts Ag/Al2O3 and Cu/Al2O3 were pressed into wafers. One hundred microL 10(6) TCID50/mL SARS-CoV, 100 microL 10(6) PFU/mL recombinant baculovirus expressing hamster's prion protein (haPrP) protein and roughly 10(6) E. coli were slowly dropped onto the surfaces of the catalyst wafers and exposed for 5 and 20 min, respectively. After eluted from the surfaces of wafers, the infectivity of viruses and propagation of bacteria were measured. The expression of PrP protein was determined by Western blot. The morphological changes of bacteria were observed by electronic microscopy. RESULTS: After exposure to the catalysts surfaces for 5 and 20 min, the infectivity of SARS-CoV in Vero cells and baculovirus in Sf9 cells dropped down to a very low and undetectable level, and no colony was detected using bacteria culture method. The expression of haPrP protein reduced to 21.8% in the preparation of Sf9 cells infected with recombinant baculovirus exposed for 5 min and was undetectable exposed for 20 min. Bacterial membranes seemed to be cracked and the cytoplasm seemed to be effluent from cell bodies. CONCLUSION: Exposures to the surfaces of Ag/Al2O3 and Cu/Al2O3 destroy the replication and propagation abilities of SARS-CoV, baculovirus and E. coli. Inactivation ability of metal catalysts needs to interact with air, utilizing oxygen molecules in air. Efficiently killing viruses and bacteria on the surfaces of the two metal catalysts has a promising potential for air-disinfection in hospitals, communities, and households.