Gene expression profile of Sox1,Sox2,p53,Bax and Nestin in neural stem cells and adult mouse brain tissues

Histone deacetylation is a key modulator involved in cell proliferation,apoptosis,and mRNA transcription.However,the effects of histone deacetylation on C17.2 neural stem cells(NSCs)remain unclear.Here,the histone deacetylase inhibitors nicotinamide and trichostatin A(TSA)were used to determine the role of histone deacetylation on gene transcription in NSCs.The results showed that the mRNA expression of p53,Sox1,Sox2,and Bax were significantly higher in E14.5 NSCs than in C17.2 NSCs.Nestin,a marker gene of neuronal differentiation,did not differ significantly between E14.5 NSCs and C17.2 NSCs.The transcription levels of p53 and Nestin were significantly higher in C17.2 NSCs than in differentiated brain tissues,and the expression of Bax,Sox1,and Sox2 was higher in the olfactory bulb than in other brain tissues.Nicotinamide and TSA treatment decreased the transcription of Sox2,p53,Nestin,and Bax in C17.2 NSCs,although the difference was statistically significant only for Sox2 and Nestin,Sox1 transcription was not detected.These results demonstrated that mRNA expression profiles differ between C17.2 NSCs,E14.5 NSCs,and adult mouse brain tissues,and HDAC inhibitors regulate gene expression by modulating histone acetylation.

The characterization of transmembrane protein 59-like(TMEM59L)reveals its role in the regulating the level of the GDI protein family

The characterization and functions of transmembrane protein 59-like(TMEM59L),a type I transmembrane protein,are not clearly understood until now.Some TMEM59L and fluorescent fusion proteins constructs were transfected in cell lines and liposomes,and their localization was observed.The effects of protein constructs were studied by fluorescence microscopy and western blotting.This study reports a novel function of human TMEM59L(hTMEM59L)related to the expression and location of some proteins.In addition,we report two novel splice variants of human TMEM59L(hTMEM59L).The localization of mutants of this protein,lacking a middle region,and a Cterminal deletion,markedly differed from that of full-length hTMEM59L.Intracellular movement assessment in living cells showed the localization of TMEM59L to vesicular structures in the Golgi bodies,and the cell membrane was observed in living cells.Overexpression of TMEM59L markedly increased the level of amyloid precursor protein because of TMEM59L-mediated inhibition of cell membrane transport but did not affect the expression of betasecretase 2.TMEM59L overexpression also significantly increased the levels of Rab GDP dissociation inhibitor alpha and Rab GDP dissociation inhibitor beta proteins.These results suggest that TMEM59L is involved in the packaging of acidic vesicles and thereby functions in the trafficking and processing of intracellular proteins.

ATP11B deficiency leads to impairment of hippocampal synaptic plasticity

Synaptic plasticity is known to regulate and support signal transduction between neurons, while synaptic dysfunction contributes to multiple neurological and other brain disorders;however, the specific mechanism underlying this process remains unclear. In the present study, abnormal neural and dendritic morphology was observed in the hippocampus following knockout of Atpllb both in vitro and in vivo. Moreover, ATP11B modified synaptic ultrastructure and promoted spine remodeling via the asymmetrical distribution of phosphatidylserine and enhancement of glutamate release, glutamate receptor expression, and intracellular Ca^2+ concentration. Fuithermoe experimental results also indicate that ATP11B regulated synaptic plasticity in hippocampal neurons through the MAPK14 signaling pathway. In conclusion, our data shed light on the possible mechanisms underlying the regulation of synaptic plasticity and lay the foundation for the exploration of proteins involved in signal transduction during this process.

Potential glioblastoma biomarkers identified by mass spectroscopy and iTRAQ labeling

Glioblastoma multiforme(GBM)is the most common primary malignant tumor of the central nervous system.Grade IV GBM is lethal,and has a high rate of relapse despite aggressive therapy.The prognosis is poor because of therapeutic resistance and tumor relapse.1 Very low rates of clinical responses and frequent treatment failures are common.Previous studies have focused on identifying genetic alterations in GBM that have diagnostic and prognostic values and may help to define the subclasses of the GBM patients,2,3 including mutations in isocitrate dehydrogenase 1(IDH1),amplification of epidermal growth factor receptors(EGFR),and mutations and polymorphisms of telomerase reverse transcriptase(TERT)promoter.These markers are useful for identifying the pathogenesis of malignant glioma formation,but they are all associated with tumorigenesis and do not currently influence the treatment of most GBM patients.

Dendritic Cell Factor 1-Knockout Results in Visual Deficit Through the GABA System in Mouse Primary Visual Cortex

The visual system plays an important role in our daily life. In this study, we found that loss of dendritic cell factor 1（DCF1） in the primary visual cortex（V1） caused a sight deficit in mice and induced an abnormal increase in glutamic acid decarboxylase 67, an enzyme that catalyzes the decarboxylation of glutamate to gamma aminobutyric acid and CO2, particularly in layer 5. In vivo electrophysiological recordings confirmed a decrease in delta, theta,and beta oscillation power in DCF1-knockout mice. This study presents a previously unknown function of DCF1 in V1, suggests an unknown contact between DCF1 and GABA systems, and provides insight into the mechanism and treatment of visual deficits.