Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nanoscale ; 14(47): 17700-17713, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36416809

RESUMO

Evaluation of Gastrointestinal Stromal Tumors (GIST) during initial clinical staging, surgical intervention, and postoperative management can be challenging. Current imaging modalities (e.g., PET and CT scans) lack sensitivity and specificity. Therefore, advanced clinical imaging modalities that can provide clinically relevant images with high resolution would improve diagnosis. KIT is a tyrosine kinase receptor overexpressed on GIST. Here, the application of a specific DNA aptamer targeting KIT, decorated onto a fluorescently labeled porous silicon nanoparticle (pSiNP), is used for the in vitro & in vivo imaging of GIST. This nanoparticle platform provides high-fidelity GIST imaging with minimal cellular toxicity. An in vitro analysis shows greater than 15-fold specific KIT protein targeting compared to the free KIT aptamer, while in vivo analyses of GIST-burdened mice that had been injected intravenously (IV) with aptamer-conjugated pSiNPs show extensive nanoparticle-to-tumor signal co-localization (>90% co-localization) compared to control particles. This provides an effective platform for which aptamer-conjugated pSiNP constructs can be used for the imaging of KIT-expressing cancers or for the targeted delivery of therapeutics.


Assuntos
Aptâmeros de Nucleotídeos , Tumores do Estroma Gastrointestinal , Animais , Camundongos , Silício , Tumores do Estroma Gastrointestinal/diagnóstico por imagem
2.
ACS Sens ; 6(2): 418-428, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33263399

RESUMO

A one-dimensional photonic crystal is prepared from porous silicon (pSi) and impregnated with a chemically specific colorimetric indicator dye to provide a self-referenced vapor sensor for the selective detection of hydrogen fluoride (HF), hydrogen cyanide (HCN), and the chemical nerve agent diisopropyl fluorophosphate (DFP). The photonic crystal is prepared with two stop bands: one that coincides with the optical absorbance of the relevant activated indicator dye and the other in a spectrally "clear" region, to provide a reference. The inner pore walls of the pSi sample are then modified with octadecylsilane to provide a hydrophobic interior, and the indicator dye of interest is then loaded into the mesoporous matrix. Remote analyte detection is achieved by measurement of the intensity ratio of the two stop bands in the white light reflectance spectrum, which provides a means to reliably detect colorimetric changes in the indicator dye. Indicator dyes were chosen for their specificity for the relevant agents: rhodamine-imidazole (RDI) for HF and DFP, and monocyanocobinamide (MCbi) for HCN. The ratiometric readout allows detection of HF and HCN at concentrations (14 and 5 ppm, respectively) that are below their respective IDLH (immediately dangerous to life and health) concentrations (30 ppm for HF; 50 ppm for HCN); detection of DFP at a concentration of 114 ppb is also demonstrated. The approach is insensitive to potential interferents such as ammonia, hydrogen chloride, octane, and the 43-component mixture of VOCs known as EPA TO-14A, and to variations in relative humidity (20-80% RH). Detection of HF and HCN spiked into the complex mixture EPA TO-14A is demonstrated. The approach provides a general means to construct robust remote detection systems for chemical agents.


Assuntos
Agentes Neurotóxicos , Silício , Corantes , Ácido Fluorídrico , Porosidade
3.
Adv Funct Mater ; 30(25)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32982626

RESUMO

Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are pre-loaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle-drug-polymer hybrids are prepared in the form of oriented poly(lactic-co-glycolic acid) nanofiber scaffolds. We test three different therapeutic payloads: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin-related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water-soluble payloads. The drug-loaded pSiNP-nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug-free control nanofibers in a dorsal root ganglion explant assay.

4.
Polymers (Basel) ; 12(4)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252257

RESUMO

Surface condition and corrosion resistance are major concerns when metallic materials are going to be utilized for applications. In this study, FeCoNiCr medium-entropy alloy (MEA) is first treated with a nitrogen atmospheric-pressure plasma jet (APPJ) and then coated with octadecyltrichlorosilane (OTS) for the surface modification. The hydrophobicity of the FeCoNiCr MEA was effectively improved by OTS-coating treatment, APPJ treatment, or the combination of both treatments (OTS-coated APPJ-treated), which increased the water contact angle from 54.49° of the bare MEA to 70.56°, 93.94°, and 88.42°, respectively. Potentiodynamic polarization and electrochemical impedance spectroscopy tests demonstrate that the APPJ-treated FeCoNiCr MEA exhibits the best anti-corrosion properties. X-ray photoelectron spectroscopy reveals that APPJ treatment at 700 °C oxidizes all the alloying elements in the FeCoNiCr MEA, which demonstrates that a short APPJ treatment of two-minute is effective in forming a metal oxide layer on the surface to improve the corrosion resistance of FeCoNiCr MEA. These results provide a convenient and rapid method for improving surface properties of FeCoNiCr MEA.

5.
Zhongguo Gu Shang ; 32(8): 727-730, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31533384

RESUMO

OBJECTIVE: To explore clinical effects of suture anchor with V-Y tenoplasty for the treatment of old Achilles tendon rupture. METHODS: From May 2014 to March 2018, 26 patients with old Achilles tendon rupture treated by suture anchor with V-Y tenoplasty, including 18 males and 8 females aged from 19 to 56 years old with an average of (36.0±11.7) years old, the courses of disease ranged from 42 to 62 days with an average of (49.0±5.3) days; the distances of Achilles tendon-shortening ranged from 2 to 7 cm with an average of (4.0±1.6) cm. Postoperative complications were observed, preoperative and postoperative American Orthopaedic Foot and Ankle Soviety(AOFAS) score were used to evaluate clinical effects. RESULTS: All patients were followed up from 8 to 18 months with an average of(12.0±2.5) months. No Achilles tendon rupture occurred again. Postoperative AOFAS score at 3 months(93.37 ±3.48) was higher than before operation(57.26±5.06)(t=9.564, P<0.05), and 14 patients got excellent results, 11 moderate and 1 poor. CONCLUSIONS: Suture anchor with V-Y tenoplasty for old Achilles tendon rupture could achieve stable fixation, relieve pain, improve walking ability and quality of life, and also recover good function of ankle joint.


Assuntos
Tendão do Calcâneo , Traumatismos dos Tendões , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ruptura , Âncoras de Sutura , Técnicas de Sutura , Resultado do Tratamento , Adulto Jovem
6.
World Neurosurg ; 120: e453-e456, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30149165

RESUMO

OBJECTIVE: We sought to develop a new posterior fusion technique composed of bilateral C1 titanium cables and C2 pedicle screw-rods for treatment of atlantoaxial instability not suitable for C1 screw placement. METHODS: A study was conducted of 18 patients with atlantoaxial instability who had C1 broken screw trajectory or anatomic anomalies. All patients underwent posterior fixation with bilateral C1 titanium cables and C2 pedicle screws. The follow-up period was a minimum 1 year. Clinical outcomes measurements included visual analog scale score for neck pain assessment, the American Spinal Injury Association Impairment Scale and Japanese Orthopaedic Association score for neurologic status and function. According to preoperative computed tomography (CT) reconstruction and CT angiography, the patients selected in this study were not suitable for C1 screw placement. Postoperative plain radiographs and CT reconstruction were performed to evaluate the reduction, bony fusion, and implant position. All outcomes were evaluated at each follow-up. RESULTS: The average clinical follow-up period was 24 months (range 12-36 months). All patients had complete neck pain relief at postoperative 6 months. Their neurologic symptoms had improved significantly at 1-year follow-up. Radiologic outcomes indicated good bony fusion and construction stability in all patients without implant failure at the last follow-up. No neural or vascular complications related to this technique were observed. CONCLUSIONS: Posterior atlantoaxial fixation using C1 titanium cables and C2 pedicle screw-rod construct appears to be an effective and safe technique for treatment of atlantoaxial instability, which could be an alternative method for cases unsuitable for C1 screw placement when using C1-C2 screw fixation.


Assuntos
Articulação Atlantoaxial/cirurgia , Vértebra Cervical Áxis/cirurgia , Atlas Cervical/cirurgia , Instabilidade Articular/cirurgia , Parafusos Pediculares , Fusão Vertebral/métodos , Adulto , Articulação Atlantoaxial/diagnóstico por imagem , Vértebra Cervical Áxis/diagnóstico por imagem , Atlas Cervical/diagnóstico por imagem , Feminino , Humanos , Instabilidade Articular/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fusão Vertebral/instrumentação , Titânio , Tomografia Computadorizada por Raios X
7.
Zhongguo Gu Shang ; 31(1): 5-11, 2018 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-29533030

RESUMO

OBJECTIVE: To compare radiographic results and clinical effects of titanium mesh cage with two endcaps(on-endcaps titanium mesh cage) and without endcaps(non-endcaps titanium mesh cage) in anterior cervical corpectomy and fusion(ACCF) for elderly cervical spondylotic myelopathy. METHODS: The clinical data of 60 patients with cervical spondylotic myelopathy underwent ACCF from January 2011 to January 2016 were retrospectively analyzed. There were 26 males and 34 females, aged from 68 to 79 years old with a mean 75.8 years old. The patients were divided into two groups according to the different titanium mesh cage, using on-endcaps titanium mesh cage(group A, 32 cases) or non-endcaps titanium mesh cage (group B, 28 cases). The nerve function was evaluated by JOA score system; the height of intervertebral fusion segments and fusion segmental lordosis angle (Cobb angle) were measured by cervical lateral X-ray films, the bone graft fusion rate of titanium mesh was evaluated by CT. RESULTS: All the patients were followed up from 1 to 2 years with an average of 1.5 years. The preoperative JOA scores of group A were 9.3±1.7, postoperative at 1 week, 3 months, 1 year were 14.2±1.8, 15.7±1.2, 15.4±1.5, respectively; and the preoperative JOA scores of group B were 9.1±1.8, postoperative at 1 week, 3 months, 1 year were 14.5±1.3, 14.9±1.7, 15.2±1.6, respectively. The postoperative JOA scores between two groups were obviously improved than that of preoperative (P<0.05). There was no significant difference in JOA scores of 3 time-point after operation between two groups (P>0.05). In the group A, preoperative intervertebral height were(42.1±2.4) mm, postoperative at 1 week, 3 months, 1 year were (45.3±3.2) mm, (44.7±2.9) mm, (44.5±3.0) mm, respectively; preoperative Cobb angle of fusion segments were (5.3±1.2)°, postoperative at 1 week, 3 months, 1 year were (10.3±1.9) °, (10.1±1.7) °, (9.9±1.3) °, respectively. And in group B, preoperative intervertebral height were (43.4±2.3)mm, postoperative at 1 week, 3 months, 1 year were (45.7±2.8) mm, (44.2±2.7) mm, (41.5±2.1) mm, respectively; preoperative Cobb angle of fusion segments were (5.4±1.0) °, postoperative at 1 week, 3 months, 1 year were (11.2±1.8)°, (10.8±1.6)°, (7.2±1.4) °, respectively. The postoperative intervertebral height, Cobb angle of fusion segments between two groups were obviously improved than that of preoperative (P<0.05). There was no significant difference in intervertebral height and Cobb angle at 1 week, 3 months after operation between two groups(P>0.05). One year after operation, intervertebral height and Cobb angle in group A was better than that of group B(P<0.05). CONCLUSIONS: On-endcaps titanium mesh cage is superior to non-endcaps titanium mesh cage in the maintenance of cervical intervebral height and segmental lordosis angle postoperatively at elderly spondylotic myelopathy complicated with osteoporosis. The usage of on-endcaps titanium mesh cage can effectively reduce postoperative subsidence rate.


Assuntos
Vértebras Cervicais/cirurgia , Osteoporose/cirurgia , Doenças da Medula Espinal/cirurgia , Espondilose/cirurgia , Titânio , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fusão Vertebral/instrumentação , Resultado do Tratamento
8.
Neuropsychopharmacology ; 40(4): 974-86, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25308353

RESUMO

Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.


Assuntos
Tonsila do Cerebelo/metabolismo , Ansiedade/patologia , Ansiedade/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Proteínas da Mielina/metabolismo , Receptor ErbB-4/metabolismo , Receptores de Superfície Celular/metabolismo , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Técnicas In Vitro , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas da Mielina/genética , Proteínas da Mielina/farmacologia , Receptor Nogo 1 , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/genética , Receptor ErbB-4/genética , Receptor ErbB-4/farmacologia , Receptores de Superfície Celular/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tirfostinas/farmacologia , Ácido gama-Aminobutírico/metabolismo
9.
Turk Neurosurg ; 24(5): 713-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25269042

RESUMO

AIM: This study aimed to evaluate the short- to medium-term outcomes of the second-generation Wallis interspinous dynamic stabilization device for treatment of lumbar degenerative disease. MATERIAL AND METHODS: Fifty patients with lumbar degenerative disease treated from August 2007 to September 2009 were included in this retrospective study. The Japanese Orthopedic Association (JOA) score and the Oswestry Disability Index (ODI) were used for therapeutic efficacy evaluation. Odom's criteria were used to evaluate postoperative outcome with regard to symptoms. Anteroposterior X-rays were obtained after surgery. All patients were followed up for 2 years. RESULTS: Based on Odom's criteria, 22, 24 and 4 patients had excellent, good, and fair results respectively. The JOA score at 3, 12, and 24 months after surgery was significantly higher than before surgery (all p < 0.001), and the ODI score at 3, 12, and 24 months after surgery was significantly lower than before surgery (all p < 0.001). The posterior intervertebral disc height and the neural foramina height at 12 and 24 months after surgery was significantly higher than before surgery (both p < 0.001). CONCLUSION: Implantation of the second-generation Wallis interspinous dynamic stabilization device produced satisfactory clinical outcome at short- and medium-term follow-up in patients with lumbar degenerative disease.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Fusão Vertebral/instrumentação , Estenose Espinal/cirurgia , Adulto , Desenho de Equipamento , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Próteses e Implantes , Radiografia , Estudos Retrospectivos , Fusão Vertebral/métodos , Estenose Espinal/diagnóstico por imagem , Resultado do Tratamento
10.
Int J Clin Exp Pathol ; 7(5): 2179-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24966926

RESUMO

Globin family was famous for oxygen supply function of its members such as hemoglobin and myoglobin. With the progress of research, several members of this protein family have been proven to play roles in tumors including glioma. Androglobin (ADGB) is a recently identified member of globin family with very few studies about its function. In the present study, we show that ADGB plays an oncogene role in glioma. Lentiviral vector mediated ADGB knockdown inhibited the proliferation of glioma cell lines determined by MTT assay and colony formation assay. ADGB knockdown also increased the apoptosis of glioma cell line U251 assessed by flow cytometry. In addition, western blot showed that ADGB knockdown altered levels of several proteins related to proliferation, survival or apoptosis in U251 cells. These findings suggest ADGB is involved in the progression of glioma in vitro.


Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Proliferação de Células , Glioma/metabolismo , Globinas/metabolismo , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas de Ligação a Calmodulina/genética , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Vetores Genéticos , Glioma/genética , Glioma/patologia , Globinas/genética , Humanos , Lentivirus/genética , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Tempo , Transfecção
11.
Int J Clin Exp Pathol ; 7(12): 8602-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25674224

RESUMO

Prostatic acid phosphatase (PAP) is expressed in nociceptive dorsal root ganglion (DRG) neurons and functions as an ectonucleotidase that dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine to suppress pain via activating A1-adenosine receptor (A1R) in dorsal spinal cord. However, the effect of peripheral nerve injury on the expression of PAP has not been reported until now. In the present study we found that PAP expression in DRG neurons is significantly decreased from the 2nd day after peripheral nerve injury and reaches the bottom at the 14th. In addition, intrathecal PAP injection can reduce mechanical allodynia induced by spared nerve injury. Our findings suggest that the decrease of PAP is involved in pathophysiological mechanisms of neuropathic pain.


Assuntos
Fosfatase Ácida/biossíntese , Neuralgia/enzimologia , Células Receptoras Sensoriais/enzimologia , Animais , Regulação para Baixo , Gânglios Espinais/enzimologia , Hiperalgesia/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Masculino , Traumatismos dos Nervos Periféricos/enzimologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
12.
Neuron ; 78(4): 644-57, 2013 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-23719163

RESUMO

Neuregulin 1 (Nrg1) is a susceptibility gene of schizophrenia, a disabling mental illness that affects 1% of the general population. Here, we show that ctoNrg1 mice, which mimic high levels of NRG1 observed in forebrain regions of schizophrenic patients, exhibit behavioral deficits and hypofunction of glutamatergic and GABAergic pathways. Intriguingly, these deficits were diminished when NRG1 expression returned to normal in adult mice, suggesting that damage which occurred during development is recoverable. Conversely, increase of NRG1 in adulthood was sufficient to cause glutamatergic impairment and behavioral deficits. We found that the glutamatergic impairment by NRG1 overexpression required LIM domain kinase 1 (LIMK1), which was activated in mutant mice, identifying a pathological mechanism. These observations demonstrate that synaptic dysfunction and behavioral deficits in ctoNrg1 mice require continuous NRG1 abnormality in adulthood, suggesting that relevant schizophrenia may benefit from therapeutic intervention to restore NRG1 signaling.


Assuntos
Ácido Glutâmico/metabolismo , Neuregulina-1/metabolismo , Prosencéfalo/metabolismo , Esquizofrenia/genética , Transmissão Sináptica/genética , Fatores Etários , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Predisposição Genética para Doença , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , Camundongos Transgênicos , Neuregulina-1/genética , Neurônios/metabolismo , Prosencéfalo/citologia , Prosencéfalo/crescimento & desenvolvimento , Esquizofrenia/metabolismo , Transmissão Sináptica/fisiologia , Distribuição Tecidual
13.
Zhongguo Gu Shang ; 25(6): 463-7, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23016380

RESUMO

OBJECTIVE: To evaluate clinical results of an interspinous stabilization system (Wallis) in treating lumbar degenerative disease in the short-term. METHODS: From August 2007 to June 2010,48 patients with lumbar degenerative disease who were treated with interspinous stabilization system, the data of patients were analyzed retrospectively. In all of the 48 cases, there were 30 males and 18 females with an average age of 54.2 years (ranged, 40 to 68 years). Forty-four cases were with single segment and 4 cases with two segments. Of them, 4 cases were in L3, 4, 40 cases were in L4, 5, 4 cases were in L3, 4 and L4, 5. The radiographic data of patients were analyzed. Clinical effects were evaluated by Japanese Orthopedic Association (JOA) score system and low back pain disability questionnaire (Oswestry) and Odom method. RESULTS: All the patients were followed up from 1 to 2 years with an average of 18 months. According to Odom's criteria, 20 cases obtained excellent results, 24 good, 4 fair. JOA score increased from 12.4 +/- 2.7 preoperatively to 26.1 +/- 2.0 postoperatively (P < 0.01). Oswestry score decreased from 14.1 +/- 2.9 preoperatively to 5.5 +/- 1.8 postoperatively (P < 0.01). The posterior height of intervertebral space and height of nerve root canal increased compared with that of preperative height. CONCLUSION: The treatment of lumbar degenerative disease with interspinous stabilization system can obtain satisfactory effects in the near future. It can retain dynamic stable of corresponding segments, expand volume of vertebral canal, and is safe and feasible.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Estenose Espinal/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Proc Natl Acad Sci U S A ; 107(50): 21818-23, 2010 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-21106764

RESUMO

Neuregulin 1 (NRG1) is a trophic factor that acts by stimulating ErbB receptor tyrosine kinases and has been implicated in neural development and synaptic plasticity. In this study, we investigated mechanisms of its suppression of long-term potentiation (LTP) in the hippocampus. We found that NRG1 did not alter glutamatergic transmission at SC-CA1 synapses but increased the GABA(A) receptor-mediated synaptic currents in CA1 pyramidal cells via a presynaptic mechanism. Inhibition of GABA(A) receptors blocked the suppressing effect of NRG1 on LTP and prevented ecto-ErbB4 from enhancing LTP, implicating a role of GABAergic transmission. To test this hypothesis further, we generated parvalbumin (PV)-Cre;ErbB4(-/-) mice in which ErbB4, an NRG1 receptor in the brain, is ablated specifically in PV-positive interneurons. NRG1 was no longer able to increase inhibitory postsynaptic currents and to suppress LTP in PV-Cre;ErbB4(-/-) hippocampus. Accordingly, contextual fear conditioning, a hippocampus-dependent test, was impaired in PV-Cre;ErbB4(-/-) mice. In contrast, ablation of ErbB4 in pyramidal neurons had no effect on NRG1 regulation of hippocampal LTP or contextual fear conditioning. These results demonstrate a critical role of ErbB4 in PV-positive interneurons but not in pyramidal neurons in synaptic plasticity and support a working model that NRG1 suppresses LTP by enhancing GABA release. Considering that NRG1 and ErbB4 are susceptibility genes of schizophrenia, these observations contribute to a better understanding of how abnormal NRG1/ErbB4 signaling may be involved in the pathogenesis of schizophrenia.


Assuntos
Receptores ErbB/metabolismo , Interneurônios/metabolismo , Potenciação de Longa Duração/fisiologia , Neuregulina-1/metabolismo , Parvalbuminas/metabolismo , Animais , Condicionamento Psicológico , Receptores ErbB/genética , Medo , Antagonistas de Receptores de GABA-A/farmacologia , Hipocampo/citologia , Hipocampo/metabolismo , Interneurônios/citologia , Potenciação de Longa Duração/efeitos dos fármacos , Camundongos , Camundongos Knockout , Neuregulina-1/genética , Receptor ErbB-4 , Receptores de GABA-A/metabolismo , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo
15.
Proc Natl Acad Sci U S A ; 107(3): 1211-6, 2010 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-20080551

RESUMO

Neuregulin 1 (NRG1) is a trophic factor thought to play a role in neural development. Recent studies suggest that it may regulate neurotransmission, mechanisms of which remain elusive. Here we show that NRG1, via stimulating GABA release from interneurons, inhibits pyramidal neurons in the prefrontal cortex (PFC). Ablation of the NRG1 receptor ErbB4 in parvalbumin (PV)-positive interneurons prevented NRG1 from stimulating GABA release and from inhibiting pyramidal neurons. PV-ErbB4(-/-) mice exhibited schizophrenia-relevant phenotypes similar to those observed in NRG1 or ErbB4 null mutant mice, including hyperactivity, impaired working memory, and deficit in prepulse inhibition (PPI) that was ameliorated by diazepam, a GABA enhancer. These results indicate that NRG1 regulates the activity of pyramidal neurons by promoting GABA release from PV-positive interneurons, identifying a critical function of NRG1 in balancing brain activity. Because both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study provides insight into potential pathogenic mechanisms of schizophrenia and suggests that PV-ErbB4(-/-) mice may serve as a model in the study of this and relevant brain disorders.


Assuntos
Receptores ErbB/fisiologia , Interneurônios/metabolismo , Neuregulina-1/fisiologia , Parvalbuminas/metabolismo , Células Piramidais/metabolismo , Animais , Receptores ErbB/genética , Interneurônios/citologia , Memória , Camundongos , Camundongos Knockout , Células Piramidais/citologia , Receptor ErbB-4 , Ácido gama-Aminobutírico/metabolismo
16.
Proc Natl Acad Sci U S A ; 104(34): 13792-7, 2007 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-17690248

RESUMO

Extensive neurogenetic analysis has shown that memory formation depends critically on cAMP-protein kinase A (PKA) signaling. Details of how this pathway is involved in memory formation, however, remain to be fully elucidated. From a large-scale behavioral screen in Drosophila, we identified the yu mutant to be defective in one-day memory after spaced training. The yu mutation disrupts a gene encoding an A-kinase anchoring protein (AKAP). AKAPs comprise a family of proteins, which determine the subcellular localization of PKAs and thereby critically restrict cAMP signaling within a cell. Further behavioral characterizations revealed that long-term memory (LTM) was disrupted specifically in the yu mutant, whereas learning, short-term memory and anesthesia-resistant memory all appeared normal. Another independently isolated mutation of the yu gene failed to complement the LTM defect associated with the yu mutation, and this phenotypic defect could be rescued by induced acute expression of a yu(+) transgene, suggesting that yu functions physiologically during memory formation. AKAP Yu is expressed preferentially in the mushroom body (MB) neuroanatomical structure, and expression of a yu(+) transgene to the MB, but not to other brain regions, is sufficient to rescue the LTM defect of the yu mutant. These observations lead us to conclude that proper localization of PKA by Yu AKAP in MB neurons is required for the formation of LTM.


Assuntos
Drosophila melanogaster/metabolismo , Memória/fisiologia , Bulbo Olfatório/metabolismo , Animais , Animais Geneticamente Modificados , Comportamento Animal , AMP Cíclico/metabolismo , Drosophila melanogaster/genética , Genótipo , Mutação/genética , Transdução de Sinais , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...