ABSTRACT
During exercise, multiple sensory information such as visual outflow, proprioception, and vestibular information promote an increase in arousal state, which may convey positive effects on cognitive abilities such as memory. Nevertheless, which of the components of the ascending arousal system (AAS) are engaged during physical activity and which of them are critical for cognitive enhancement, induced by exercise is still unclear. Two experiments were conducted, to answer these questions: in the first one, the neuronal activity of different components of the AAS was evaluated by c-Fos immunoreactivity (Fos-ir) in running rats exposed to a lock or unlock running wheel. We found a specific Fos-ir increase in the tuberomammillary nucleus (TMN) associated with physical exercise. In the second experiment sedentary and exercised rats were challenged to conduct an object recognition memory task, and the activity of the AAS after learning was evaluated by c-Fos immunoreactivity. The exercised group showed a higher performance in the object recognition memory task which gets correlated with an increase on Fos-ir in the TMN, but not with the other components of the AAS, suggesting that the increase on TMN activity induced by exercise may be the foremost contributor of the AAS to memory enhancement observed in exercised animals.
Subject(s)
Memory/physiology , Physical Conditioning, Animal/physiology , Proto-Oncogene Proteins c-fos/genetics , Animals , Arousal/physiology , Brain/physiology , Cognition/physiology , Gene Expression Regulation/genetics , Gene Expression Regulation/physiology , Hypothalamic Area, Lateral/physiology , Learning/physiology , Male , Motor Activity/physiology , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
Pharmacological activation of autophagy is becoming an attractive strategy to induce the selective degradation of aggregate-prone proteins. Recent evidence also suggests that autophagy impairment may underlie the pathogenesis of several neurodegenerative diseases. Mutations in the gene encoding SOD1 (superoxide disumutase 1) trigger familial amyotrophic lateral sclerosis (ALS), inducing its misfolding and aggregation and the progressive loss of motoneurons. It is still under debate whether autophagy has a protective or detrimental role in ALS. Here we evaluate the impact of BECN1/Beclin 1, an essential autophagy regulator, in ALS. BECN1 levels were upregulated in both cells and animals expressing mutant SOD1. To evaluate the impact of BECN1 to the pathogenesis of ALS in vivo, we generated mutant SOD1 transgenic mice heterozygous for Becn1. We observed an unexpected increase in life span of mutant SOD1 transgenic mice haploinsufficient for Becn1 compared with littermate control animals. These effects were accompanied by enhanced accumulation of SQSTM1/p62 and reduced levels of LC3-II, and an altered equilibrium between monomeric and oligomeric mutant SOD1 species in the spinal cord. At the molecular level, we detected an abnormal interaction of mutant SOD1 with the BECN1-BCL2L1 complex that may impact autophagy stimulation. Our data support a dual role of BECN1 in ALS and depict a complex scenario in terms of predicting the effects of manipulating autophagy in a disease context.
Subject(s)
Amyotrophic Lateral Sclerosis/etiology , Amyotrophic Lateral Sclerosis/pathology , Apoptosis Regulatory Proteins/metabolism , Animals , Astrocytes/metabolism , Astrocytes/pathology , Autophagy , Beclin-1 , Biomarkers/metabolism , Disease Models, Animal , Gene Targeting , Haploinsufficiency , Heterozygote , Humans , Mice, Inbred C57BL , Mice, Transgenic , Models, Biological , Motor Neurons/metabolism , Motor Neurons/pathology , Mutant Proteins/metabolism , Mutation , Protein Aggregates , Protein Binding , Protein Multimerization , Superoxide Dismutase/metabolism , Up-Regulation , bcl-X Protein/metabolismABSTRACT
El objetivo del presente trabajo de investigación es la descripción del protocolo para la rehabilitación protésica implanto asistida de carga inmediata, en sujetos desdentados completos maxilares o mandibulares utilizando una "Cubeta protésica Multifuncional Uchile". El protocolo fue desarrollado en un grupo de 96 sujetos desdentados completos mandibulares y/o maxilares, distribuidos en 42 hombres y 54 mujeres con un promedio de edad de 61.5 años, a los cuales se les efectúa un tratamiento protésico implanto asistido, bajo la modalidad de prótesis hibrida en distribución poligonal de arco completo instalada dentro de las 48 hrs. siguientes a la inserción de los implantes, tomado una impresión post quirúrgica para la confección de la prótesis de carga inmediata mediante una cubeta protésica multifuncional Uchile .Terminada la cirugía de inserción de implantes, se verifican los Torques quirúrgicos de inserción implantario y los valores de cuociente de estabilidad implantaria (ISQ), procediendo a la toma inmediata de una impresión mediante la técnica de cubeta multifuncional UChile, la cual permite registrara , la altura facial inferior del rostro , el posicionamiento de los implantes , el posicionamiento de la topografía gingival y su máxima intercuspidación .Se envía al laboratorio dental para la confección de una prótesis hibrida que incluye una barra rígida de titanio de sección circular de 3 mm. de diámetro soldada ferulizando los implantes. Durante la inserción protésica se verifica el ajuste pasivo, clínico y radiográfico de la estructura metálica, se efectúa el control oclusal y el control del contorno protésico estético.Se instalaron un total de 96 prótesis de carga inmediata sobre 436 implantes con un torque de inserción quirúrgico promedio de 40.45 N, y un valor promedio de ISQ de 58.6. No se registraron secciones de barra por desajustes, sólo se efectuaron ajustes oclusales menores y eliminación de sobre contornos protésicos. La rehabilitación protésica implanto asistida de carga inmediata en sujetos desdentados completos, utilizando la cubeta Protésica multifuncional UChile, en maxila o mandíbula desdentada, presenta un resultado clínico predecible y reproducible, observando exactitud y pasividad de la estructura protésica a instalar.
The purpose of this research is the description of the protocol for implant-assisted prosthetic rehabilitation immediately loaded in edentulous subjects maxillary or mandibular complete using a "Multifunctional tray Prosthetic Uchile". The protocol was developed in a group of 96 subjects complete edentulous mandible and / or maxilla, distributed in 42 men and 54 women with an average age of 61.5 years, which makes them assisted implant prosthetic treatment, the form of distribution polygonal hybrid prosthesis in full arch installed within 48 hrs. after insertion of the implant an impression post surgical taken for making the prosthesis immediately loaded a multifunctional tray prosthetic Uchile. After surgery the implant insertion, the torques are verified surgical implant insertion quotient values and implant stability (ISQ), proceeding to the immediate seizure of a print by UChile multifunctional tray technique, which allows recorded, the lower face facial height, positioning of the implants, the positioning of the gingival topography and its maximum intercuspation. It is sent to the dental lab for the fabrication of a hybrid prosthesis including a rigid bar titanium circular section of 3 mm. splinting welded diameter implants. During insertion prosthetic passive fit is verified, clinical and radiographic metal structure, control is effected occlusal and prosthetic contour control estético. Installed a total of 96 immediately loaded prosthesis on implants with a torque 436 Average surgical insertion of 40.45 N, and an average value of 58.6 ISQ. There were no bar sections by mismatches, only minor adjustments were made occlusal and prosthetic removal on contours. The implant-assisted prosthetic rehabilitation of edentulous subjects immediate loading in full, using the multipurpose tray UChile Prosthetics in edentulous maxilla or mandible presents a predictable and reproducible clinical outcome, noting accuracy and passivity of the prosthetic structure installed.
