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1.
Nat Commun ; 15(1): 4941, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866781

RESUMEN

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced ( https://github.com/dbsb-juntendo/descSPIM ), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies.


Asunto(s)
Encéfalo , Imagenología Tridimensional , Microscopía Fluorescente , Animales , Ratones , Encéfalo/diagnóstico por imagen , Humanos , Microscopía Fluorescente/métodos , Microscopía Fluorescente/instrumentación , Imagenología Tridimensional/métodos , Línea Celular Tumoral
2.
Sci Rep ; 8(1): 2459, 2018 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-29410497

RESUMEN

Thalidomide was originally used as a sedative and found to be a teratogen, but now thalidomide and its derivatives are widely used to treat haematologic malignancies. Accumulated evidence suggests that thalidomide suppresses nerve cell death in neurologic model mice. However, detailed molecular mechanisms are unknown. Here we examined the molecular mechanism of thalidomide's neuroprotective effects, focusing on its target protein, cereblon (CRBN), and its binding protein, AMP-activated protein kinase (AMPK), which plays an important role in maintaining intracellular energy homeostasis in the brain. We used a cerebral ischemia rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Thalidomide treatment significantly decreased the infarct volume and neurological deficits of MCAO/R rats. AMPK was the key signalling protein in this mechanism. Furthermore, we considered that the AMPK-CRBN interaction was altered when neuroprotective action by thalidomide occurred in cells under ischemic conditions. Binding was strong between AMPK and CRBN in normal SH-SY5Y cells, but was weakened by the addition of H2O2. However, when thalidomide was administered at the same time as H2O2, the binding of AMPK and CRBN was partly restored. These results suggest that thalidomide inhibits the activity of AMPK via CRBN under oxidative stress and suppresses nerve cell death.


Asunto(s)
Proteínas Quinasas Activadas por AMP/genética , Proteasas ATP-Dependientes/genética , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/tratamiento farmacológico , Talidomida/farmacología , Complejos de Ubiquitina-Proteína Ligasa/genética , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/metabolismo , Proteasas ATP-Dependientes/antagonistas & inhibidores , Proteasas ATP-Dependientes/metabolismo , Animales , Isquemia Encefálica/enzimología , Isquemia Encefálica/genética , Isquemia Encefálica/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Reposicionamiento de Medicamentos , Regulación de la Expresión Génica , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/farmacología , Inmunosupresores/farmacología , Infarto de la Arteria Cerebral Media/enzimología , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/patología , Masculino , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Transducción de Señal , Complejos de Ubiquitina-Proteína Ligasa/antagonistas & inhibidores , Complejos de Ubiquitina-Proteína Ligasa/metabolismo
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