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2.
Med Phys ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705768

RESUMO

PURPOSE: Although carbon-ion therapy is becoming increasingly attractive to the treatment of tumors, details about the ionization pattern formed by therapeutic carbon-ion beam in tissue have not been fully investigated. In this work, systematic calculations for the nanodosimetric quantities and RBE of a clinically relevant carbon-ion beam were studied for the first time. METHODS: The method combining both track structure and condensed history Monte Carlo (MC) simulations was adopted to calculate the nanodosimetric quantities. Fragments and energy spectra at different positions of the radiation field of a clinically relevant carbon-ion pencil beam were generated by means of MC simulations in water. Nanodosimetric quantities such as mean ionization cluster size ( M 1 ), the first moment of conditional cluster size ( M 1 C 2 ), cumulative probability ( F 2 ) and conditional cumulative probability ( F 3 C 2 ) at these positions were then acquired based on the spectra and the pre-calculated nanodosimetric database created by track structure MC simulations. What's more, a novel approach to calculate RBE based on the said nanodosimetric quantities was introduced. The RBE calculations were then conducted for the carbon-ion beam at different water-equivalent depths. RESULTS: Lateral distributions at various water-equivalent depths of both the nanodosimetric quantities and RBE values were obtained. The values of M 1 , M 1 C 2 , F 2 and F 3 C 2 were 1.49, 2.67, 0.30 and 0.38 at the plateau at the beam central axis and maximized at 2.79, 5.69, 0.47 and 0.68 at the depths around the Bragg peak, respectively. At a given depth, M 1 and F 2 decreased laterally with increasing the distance to the beam central axis while M 1 C 2 and F 3 C 2 remained nearly unchanged at first and then decreased except for M 1 C 2 at the rising edge of the Bragg peak. The calculated RBE values were 1.07 at the plateau and 3.13 around the Bragg peak. Good agreement between the calculated RBE values and experimental data was obtained. CONCLUSIONS: Different nanodosimetric quantities feature the track structure of therapeutic carbon-ion beam in different manners. Detailed ionization patterns generated by carbon-ion beam could be characterized by nanodosimetric quantities. Moreover, the combined method adopted in this work to calculate nanodosimetric quantities is not only valid but also convenient. Nanodosimetric quantities are significantly helpful for the RBE calculations in carbon-ion therapy.

3.
Brain Res ; : 146537, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672473

RESUMO

Higher visual centers could modulate visually-guided ocular growth, in addition to local mechanisms intrinsic to the eye. There is evidence that such central modulations could be species (even subspecies)-dependent. While the mouse has recently become an important experimental animal in myopia studies, it remains unclear whether and how visual centers modulate refractive development in mice, an issue that was examined in the present study. We found that optic nerve crush (ONC), performed at P18, could modify normal refractive development in the C57BL/6 mouse raised in normal visual environment. Unexpectedly, sham surgery caused a steeper cornea, leading to a modest myopic refractive shift, but did not induce significant changes in ocular axis length. ONC caused corneal flattening and re-calibrated the refractive set-point in a bidirectional manner, causing significant myopic (<-3 D, 54.5%) or hyperopic (>+3 D, 18.2%) shifts in refractive error in most (totally 72.7%) animals, both due to changes in ocular axial length. ONC did not change the density of dopaminergic amacrine cells, but increased retinal levels of dopamine and DOPAC. We conclude that higher visual centers are likely to play a role in fine-tuning of ocular growth, thus modifying refractive development in the C57BL/6 mouse. The changes in refractive error induced by ONC are accounted for by alternations in multiple ocular dimensions, including corneal curvature and axial length.

4.
Cells ; 8(10)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597348

RESUMO

BACKGROUND: Recently, human adipose-derived stem cells (hASCs) were discovered in the human subcutaneous adipose tissue. PLTMax Human Platelet Lysate (PLTMax), a supplement refined from human platelets, has been reported to have proliferative effects on bone marrow mesenchymal stem cells. The proliferative effects of PLTMax on ASCs were investigated in this study. METHODS: The ASCs in DMEM (serum-free), DMEM+PLTMax (1%, 2%, 5%, and 10%), and DMEM+FBS (10%) were cultivated for two, five, and seven days. The cell growth rate was examined, BrdU incorporation, and the cell cycle and Ki-67 immunostaining were performed. The cell growth rate was investigated when each inhibitor (PD98059, SP600125, SB203580, and LY294002) was added and phosphorylation of ERK1/2, JNK, p38, and Akt were examined by western blotting. The cell surface marker of hASCs was also analyzed. RESULTS: The cells in the PLTMax (5%) group showed significantly more proliferation compared to the cells in control (serum-free) and FBS (10%) groups, and a significant increase in the number of cells in the S phase and G2/M phase. The number of Ki-67 positive cells increased significantly in the DMEM+ PLTMax (5%) and the FBS (10%) groups. The addition of inhibitors PD98059, SP600125, SB203580, and LY294002 decreased the proliferative effects of PLTMax on ASCs. Phosphorylation of ERK1/2, JNK, p38, and Akt was observed in both the PLTMax (5%) and the FBS (10%) groups. CONCLUSIONS: For human adipose stem cells, 5% PLTMax was the optimum concentration, which showed a significantly higher proliferative effect than 10% FBS. PLTMax is a useful medium additive, which can substitute FBS. The proliferative effects of PLTMax are suggested to function via multiple signaling pathways, similar to FBS.

5.
PLoS One ; 14(10): e0222702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600235

RESUMO

Slope one is a popular recommendation algorithm due to its simplicity and high efficiency for sparse data. However, it often suffers from under-fitting since the global information of all relevant users/items are considered. In this paper, we propose a new scheme called enhanced slope one recommendation through local information embedding. First, we employ clustering algorithms to obtain the user clusters as well as item clusters to represent local information. Second, we predict ratings using the local information of users and items in the same cluster. The local information can detect strong localized associations shared within clusters. Third, we design different fusion approaches based on the local information embedding. In this way, both under-fitting and over-fitting problems are alleviated. Experiment results on the real datasets show that our approaches defeats slope one in terms of both mean absolute error and root mean square error.

6.
Anticancer Drugs ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31503013

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors therapy, such as gefitinib, have proven to be effective for lung adenocarcinoma with epidermal growth factor receptor-sensitive mutations. However, drug resistance remains inevitable and the underlying mechanisms are still elusive and poorly understood. In order to explore the mechanisms underlying tyrosine kinase inhibitors resistance, we used long non-coding RNA microarray analysis and found that long non-coding RNA H19 was highly expressed in gefitinib-resistant cell lines. In addition, knockdown of long non-coding RNA H19 was found to be able to decrease cell proliferation, half maximal inhibitory concentration (IC50) of gefitinib, migration and invasion. Mechanistically, we demonstrated that long non-coding RNA H19 positively regulated dimethylarginine dimethylaminohydrolase-1 expression via sponging miR-148b-3p. Furthermore, overexpression or inactivation of miR-148b-3p could enhance or reverse the inhibitory effect of long non-coding RNA H19 inhibition in lung adenocarcinoma cells, respectively. High expression of either long non-coding RNA H19 or dimethylarginine dimethylaminohydrolase-1 was associated with poorer overall survival in patients with lung adenocarcinoma, while high expression of miR-148b was associated with better overall survival. Overall, our data revealed that long non-coding RNA H19 confers resistance to gefitinib via miR-148b/dimethylarginine dimethylaminohydrolase-1 axis in lung adenocarcinoma, which offers a new insight into the epidermal growth factor receptor tyrosine kinase inhibitors therapy resistance.

7.
J Cell Mol Med ; 23(11): 7406-7416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31475784

RESUMO

Achilles tendon injury is one of the challenges of sports medicine, the aetiology of which remains unknown. For a long time, estrogen receptor ß (ERß) has been known as a regulating factor of the metabolism in many connective tissues, such as bone, muscle and cartilage, but little is known about its role in tendon. Recent studies have implicated ERß as involved in the process of tendon healing. Tendon-derived stem cells (TDSCs) are getting more and more attention in tendon physiological and pathological process. In this study, we investigated how ERß played a role in Achilles tendon healing. Achilles tendon injury model was established to analyse how ERß affected on healing process in vivo. Cell proliferation assay, Western blots, qRT-PCR and immunocytochemistry were performed to investigate the effect of ERß on TDSCs. Here, we showed that ERß deletion in mice resulted in inferior gross appearance, histological scores and, most importantly, increased accumulation of adipocytes during the early tendon healing which involved activation of peroxisome proliferator-activated receptor γ (PPARγ) signalling. Furthermore, in vitro results of ours confirmed that the abnormity might be the result of abnormal TDSC adipogenic differentiation which could be partially reversed by the treatment of ERß agonist LY3201. These data revealed a role of ERß in Achilles tendon healing for the first time, thereby providing a new target for clinical treatment of Achilles tendon injury.

8.
ACS Synth Biol ; 8(10): 2194-2202, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31525995

RESUMO

The emergence of genome editing technology based on the CRISPR/Cas system enabled revolutionary progress in genetic engineering. Double-strand breaks (DSBs), which can be induced by the CRISPR/Cas9 system, cause serious DNA damage that can be repaired by a homologous recombination (HR) system or the nonhomologous end joining (NHEJ) pathway. However, many bacterial species have a very weak HR system. Thus, the NHEJ pathway can be used in prokaryotes. Starting with a brief introduction of the mechanism of the NHEJ pathway, this review focuses on current research and details of applications of NHEJ in eukaryotes, which forms the theoretical basis for the application of the NHEJ system in prokaryotes.

9.
Small ; 15(46): e1903746, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553140

RESUMO

Lactic acid (LA) is a powerful molecule as the metabolic driver in tumor microenvironments (TMEs). Inspired by its high intratumoral level (5-20 µmol g-1 ), a novel treatment paradigm via the cascade release of H2 O2 and ·OH from the LA generated by tumor metabolism is developed for catalytic and pH-dependent selective tumor chemotherapy. By utilizing the acidity and overexpression of LA within the TME, the constructed lactate oxidase (LOD)-immobilized Ce-benzenetricarboxylic acid (Ce-BTC) metal organic framework enables the intratumoral generation of ·OH via a cascade reaction: 1) the in situ catalytic release of H2 O2 from LA by LOD, and 2) the catalytic production of ·OH from H2 O2 by Ce-BTC with peroxidase-like activity. Highly toxic ·OH effectively induces tumor apoptosis/death. A new strategy for selective tumor chemotherapy is provided herein.

11.
Mol Nutr Food Res ; 63(18): e1801407, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31298459

RESUMO

SCOPE: Alzheimer's disease (AD) is a detrimental neurodegenerative disease and has no known effective treatment. The essential nutrient choline potentially plays an important role in cognition. Perinatal choline supplementation (CS) is critical for memory performance. Findings have shown that postnatal choline-containing compounds enhance memory functions in populations with memory impairments. However, whether CS can be targeted to decelerate the progression of AD remains unknown. METHODS AND RESULTS: APP/PS1 mice and their wild-type littermates are fed either a control or CS diet from 2 to 11 months of age. As compared to WT mice, APP/PS1 mice on the control diet are characterized by the reduction in the number of cholinergic neurons in the basal forebrain, reduced cholinergic fiber staining intensity in the amygdala, and reduced hippocampal and cerebral cortical levels of choline and acetylcholine. CS partially prevents these changes and ameliorates cognitive deficits and anxiety. Furthermore, amyloid-ß deposition and microgliosis are decreased in the APP/PS1 mice fed a CS diet. These effects may have been due to inhibition of NLRP3 inflammasome activation and restoration of synapse membrane formation. CONCLUSION: These findings reveal a beneficial effect of CS on AD progression during adulthood and provide a likely therapeutic intervention for AD patients.

12.
Inorg Chem ; 58(15): 9567-9571, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31305083

RESUMO

Two new Krebs-type tungstoantimonates (H2en)8H6{[Sb2(WO2)2(B-ß-SbW9O33)2][(WO2)2(WO3)2(B-ß-SbW9O33)2]}·22H2O (1) and (H2en)7[(WO2)2(WO3)2(B-ß-SbW9O33)2]·12H2O (2) were synthesized and characterized. Notably, crystal 1 possesses a specific pseudo-seesaw SbO4 subunit in the central metal belt of [Sb2(WO2)2(B-ß-SbW9O33)2]12- species, which is rare in reported Krebs-type polyoxometalates. One of the structural features is that there are two kinds of Krebs-type polyanionic clusters in crystal 1 labeled as {(WO2)2(WO3)2(B-ß-SbW9O33)2} (part A) and {Sb2(WO2)2(B-ß-SbW9O33)2} (part B), respectively. The subunits A and B are alternately connected through Sb-O-W bonds into a chain-like structure of inorganic clusters. Moreover, the catalytic property of crystals 1 and 2 for electron-transfer reaction were investigated by transferring K3[Fe(CN)6] into K4[Fe(CN)6].

13.
Parasitol Res ; 118(9): 2729-2734, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321521

RESUMO

Enterocytozoon bieneusi is a zoonotic parasite which is considered to be an opportunistic pathogen of humans and animals. A number of studies have reported E. bieneusi infection in various animals. However, no information is available on the occurrence of E. bieneusi in Tan sheep, a unique indigenous sheep species in the Ningxia Hui Autonomous Region, China. The objectives of the present study were to examine the prevalence and identify the genotypes of E. bieneusi in Tan sheep in China. A total of 1014 fecal specimens of Tan sheep from six farms in the Ningxia Hui Autonomous Region were examined by nested PCR amplification of the internal transcribed spacer (ITS) of nuclear ribosomal DNA. The total prevalence of E. bieneusi was 12.2% (124/1014), ranging from 0.5 to 22.2% on six farms. Sequence analysis identified 10 genotypes of E. bieneusi, including three known genotypes, BEB6, COS-I, and CHG13, and seven novel genotypes designated as NX1 to NX7, which all belonged to group 2 by phylogenetic analysis. This is the first report describing the prevalence of E. bieneusi in Tan sheep, and the new genotypes identified in the current study expand the genotype distribution of E. bieneusi. These findings provide baseline data and have implications for the epidemiology and control of E. bieneusi infection in Tan sheep.

14.
J Am Chem Soc ; 141(29): 11353-11357, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31290659

RESUMO

Effective activation of CO2 is a prerequisite for efficient utilization of CO2 in organic synthesis. Precisely controlling the interfacial events of solids shows potential for activation. Herein, defect-enriched CeO2 with constructed interfacial frustrated Lewis pairs (FLPs, two adjacent Ce3+···O2-) effectively activates CO2 via the interactions between C/Lewis basic lattice O2- and the two O atoms in CO2/two adjacent Lewis acidic Ce3+ ions. Selective cyclic carbonate production from a catalytically tandem protocol of olefins and CO2 is used to demonstrate FLP-inspired CO2 activation.

15.
Lipids Health Dis ; 18(1): 147, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272481

RESUMO

BACKGROUND: Elevated serum uric acid is commonly associated with high triglyceride. However, the relation of triglyceride and hyperuricemia in different gender and age groups is currently not well understood. This study aimed to evaluate age- and gender-related association of high triglyceride with hyperuricemia in a subgroup of Chinese population. METHODS: We retrospectively analyzed physical examination data of 24,438 subjects (12,557 men and 11,881 women) in Kaifeng, China. The alanine aminotransferase, γ-glutamyl transpeptidase, serum creatinine, blood urea nitrogen, total cholesterol, high-density lipoprotein cholesterol, triglyceride and serum uric acid were measured in all subjects. The triglyceride was categorized into < 1.21, 1.21 ~, 1.7 ~, 2.83 ~ and >  5.6 mmol/L subgroups, and odds ratio (OR) and 95% confidence interval (CI) of hyperuricemia were calculated by logistic regression analysis. RESULTS: Univariate and age-adjusted analyses showed that high triglyceride was positively associated with hyperuricemia (p <  0.01). Further age-stratified analysis showed that the positive association was significant in the 20 ~, 30 ~, 40 ~, 50 ~, 60 ~ and 80 ~ age groups in men. In women, no statistically significant was found in 60 ~ and 70 ~ age groups. CONCLUSION: High triglyceride is positively associated with hyperuricemia in both men and women, and this association is age-related, especially in women.

16.
Respir Res ; 20(1): 163, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331325

RESUMO

BACKGROUND: Pulmonary fibrosis is a progressive and irreversible disease for which therapeutic options are currently limited. A recent in vivo study showed that tenofovir, a nucleotide analogue reverse transcriptase inhibitor, had direct antifibrotic effects on skin and liver fibrosis. Another study in vitro revealed that NS5ATP9 inhibited the activation of human hepatic stellate cells. Because of the similarity of fibrotic diseases, we hypothesized that tenofovir alafenamide fumarate (TAF), the prodrug of tenofovir, and NS5ATP9, is related to and plays a role in the suppression of pulmonary fibrosis. METHODS: We investigated the influence of NS5ATP9 on fibrosis in vitro. Human lung fibroblasts (HFL1) were transfected with short interfering RNAs or overexpression plasmids of NS5ATP9 before stimulation by human recombinant transforming growth factor-ß1. The effect of TAF was evaluated in a bleomycin-induced fibrosis murine model. Male C57BL/6 mice were treated with bleomycin on day 0 by intratracheal injection and intragastrically administered TAF or vehicle. Left lung sections were fixed for histological analysis, while homogenates of the right lung sections and HFL1 cells were analyzed by western blotting and quantitative reverse transcription polymerase chain reaction. RESULTS: NS5ATP9 suppressed the activation of lung fibroblasts. Upregulation of collagen type 3 (α 1 chain) and α-smooth muscle actin was observed in HFL1 cells when NS5ATP9 was silenced, and vice-versa. TAF also showed anti-fibrotic effects in mice, as demonstrated by histological analysis of fibrosis and expression of extracellular matrix components in the lung sections. Additionally, TAF inhibited transforming growth factor-ß1 and phosphorylated-Smad3 synthesis in HFL1 cells and the murine model, which was accompanied by upregulation of NS5ATP9. CONCLUSIONS: Our results suggest that NS5ATP9 forms a negative feedback pathway in pulmonary fibrosis and TAF has anti-fibrotic properties as it upregulates the expression level of NS5ATP9. As TAF has been shown to be safe and well-tolerated in humans, TAF and NS5ATP9 may be useful for developing novel therapeutics for pulmonary fibrosis.

17.
Mediators Inflamm ; 2019: 5796491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354386

RESUMO

Escherichia coli Nissle 1917 (EcN), a kind of probiotic, has been reported to have a protective effect on the intestinal barrier function and can ameliorate certain gastrointestinal disorders. In this study, the potential protective effect of EcN on the intestinal barrier function in a septic mouse model induced by cecal ligation and puncture (CLP) operation was investigated. FITC-Dextran 4,000 Da (FD-4) flux and the expression levels of tight junction (TJ) proteins were measured to evaluate the protective effect of EcN on the intestinal barrier function. Then, Caco-2 monolayers were utilized to further investigate the protective effect of the EcN supernatant (EcNsup) on the barrier dysfunction induced by TNF-α and IFN-γ in vitro; the plasma level of both the cytokines increased significantly during sepsis. Transepithelial electrical resistance (TEER) and FD-4 transmembrane flux were measured, and the localization of ZO-1 and Occludin was investigated by immunofluorescence. The expression of MLCK and the phosphorylation of MLC were detected by western blot. The activation of NF-κB was explored by immunofluorescence, and CHIP assays were performed to investigate the conjunction of NF-κB with the promoter of MLCK. The results indicated that EcN protected the intestinal barrier function in sepsis by ameliorating the altered expression and localization of TJ proteins and inhibiting the NF-κB-mediated activation of the MLCK-P-MLC signaling pathway which might be one of the mechanisms underlying the effect of EcN.

18.
J Nutr ; 149(9): 1543-1552, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31174208

RESUMO

BACKGROUND: Traumatic brain injury (TBI) causes dysbiosis and intestinal barrier disruption, which further exacerbate brain damage via an inflammatory pathway. Gut microbiota remodeling by Lactobacillus acidophilus (LA) is a potential intervention. OBJECTIVE: The aim of this study was to investigate the neuroprotective effects of LA in TBI and elucidated underlying mechanisms. METHODS: C57BL/6 male mice (aged 8-9 wk) were subjected to weight-drop impact and gavaged with saline (TBI + vehicle) or LA (1 × 1010 CFU) (TBI + LA) on the day of injury and each day after for 1, 3, or 7 d. The sham + vehicle mice underwent craniotomy without brain injury and were gavaged with saline. Sensorimotor functions were determined pre-TBI and 1, 3, and 7 d postinjury. Indexes of neuroinflammation, peripheral inflammation, and intestinal barrier function were measured on days 3 and 7. Microbiota composition was measured 3 d postinjury. The data were mainly analyzed by 2-factor ANOVA. RESULTS: Compared with sham + vehicle mice, the TBI + vehicle mice exhibited impairments in the neurological severity score (+692%, day 3; +600%, day 7) and rotarod test (-58%, day 3; -45%, day 7) (P < 0.05), which were rescued by LA. The numbers of microglia (total and activated) and astrocytes and concentrations of TNF-α and IL1-ß in the perilesional cortex were elevated in the TBI + vehicle mice on day 3 or 7 compared with sham + vehicle mice (P < 0.05) and were normalized by LA. Compared with sham + vehicle mice, the TBI + vehicle mice exhibited increased serum concentrations of endotoxin and TNF-α, and intestinal barrier permeability (D-lactate) on days 3 and 7 (P < 0.05), and these changes were alleviated by LA. Three days postinjury, the microbiota composition was disrupted in the TBI + vehicle mice compared with sham + vehicle mice (P < 0.05), which was restored by LA. CONCLUSION: Our results demonstrate that LA exerts neuroprotective effects that may be associated with gut microbiota remodeling in TBI mice.

19.
Connect Tissue Res ; 60(6): 507-520, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31203665

RESUMO

Over the last decade, stem cells have drawn extensive attention from scientists due to their full potential in tissue engineering, gene therapy, and cell therapy. Adipose-derived stem cells (ADSCs), which represent one type of mesenchymal stem cell (MSC), hold great promise in bone tissue engineering due to their painless collection procedure, their ability to self-renew and their multi-lineage differentiation properties. Major epigenetic mechanisms, which involve DNA methylation, histone modifications and RNA interference (RNAi), are known to represent one of the determining factors of ADSC fate and differentiation. Understanding the epigenetic modifications of ADSCs may provide a clue for improving stem cell therapy in bone repair and regeneration. The aim of this review is to present the recent advances in understanding the epigenetic mechanisms that facilitate ADSC differentiation into an osteogenic lineage, in addition to the characteristics of the main epigenetic modifications.

20.
Aging (Albany NY) ; 11(10): 3280-3297, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147527

RESUMO

Degeneration of the dopaminergic neurons in the substantia nigra and the resultant dopamine depletion from the striatum are the hallmarks of Parkinson's disease (PD) and are responsible for the disease's cardinal motor symptoms. The transcriptional repressor Neuron-Restrictive Silencer Factor (NRSF), also known as RE1-Silencing Transcription Factor (REST), was originally identified as a negative regulator of neuron-specific genes in non-neuronal cells. Our previous study showed that mice deficient in neuronal NRSF/REST expression were more vulnerable to the noxious effects of the dopaminergic neurotoxin MPTP. Here, we found that brain-specific deletion of NRSF/REST led to more severe damages to the nigrostriatal pathway and long-lasting behavioral impairments in mice challenged with MPTP. Moreover, compared to wild-type controls, these mice showed increased neurogenesis shortly after MPTP exposure, but reduced neurogenesis later on. These results suggest that NRSF/REST acts as a negative modulator of neurogenesis and a pro-survival factor of neural stem cells under both normal conditions and during the course of PD.

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