D-β-Hydroxybutyrate Is Protective in Mouse Models of Huntington's Disease

Abnormalities in mitochondrial function and epigenetic regulation are thought to be instrumental in Huntington's disease (HD), a fatal genetic disorder caused by an expanded polyglutamine track in the protein huntingtin. Given the lack of effective therapies for HD, we sought to assess the neuroprotective properties of the mitochondrial energizing ketone body, D-β-hydroxybutyrate (DβHB), in the 3-nitropropionic acid (3-NP) toxic and the R6/2 genetic model of HD. In mice treated with 3-NP, a complex II inhibitor, infusion of DβHB attenuates motor deficits, striatal lesions, and microgliosis in this model of toxin induced-striatal neurodegeneration. In transgenic R6/2 mice, infusion of DβHB extends life span, attenuates motor deficits, and prevents striatal histone deacetylation. In PC12 cells with inducible expression of mutant huntingtin protein, we further demonstrate that DβHB prevents histone deacetylation via a mechanism independent of its mitochondrial effects and independent of histone deacetylase inhibition. These pre-clinical findings suggest that by simultaneously targeting the mitochondrial and the epigenetic abnormalities associated with mutant huntingtin, DβHB may be a valuable therapeutic agent for HD

CART Peptide Is a Potential Endogenous Antioxidant and Preferentially Localized in Mitochondria

The multifunctional neuropeptide Cocaine and Amphetamine Regulated Transcript (CART) is secreted from hypothalamus, pituitary, adrenal gland and pancreas. It also can be found in circulatory system. This feature suggests a general role for CART in different cells. In the present study, we demonstrate that CART protects mitochondrial DNA (mtDNA), cellular proteins and lipids against the oxidative action of hydrogen peroxide, a widely used oxidant. Using cis-parinaric acid as a sensitive reporting probe for peroxidation in membranes, and a lipid-soluble azo initiator of peroxyl radicals, 2,2′-Azobis(2,4-dimethylvaleronitrile) we found that CART is an antioxidant. Furthermore, we found that CART localized to mitochondria in cultured cells and mouse brain neuronal cells. More importantly, pretreatment with CART by systemic injection protects against a mouse oxidative stress model, which mimics the main features of Parkinson's disease. Given the unique molecular structure and biological features of CART, we conclude that CART is an antioxidant peptide (or antioxidant hormone). We further propose that it may have strong therapeutic properties for human diseases in which oxidative stress is strongly involved such as Parkinson's disease

Fatores intrínsecos do custo energético da locomoção durante a natação Factores intrínsecos del desgaste energético de locomoción durante la natación Intrinsic factors of the locomotion energy cost during swimming

A quantidade de energia metabólica gasta em transportar a massa corporal de um sujeito por unidade de distância tem sido definida como custo energético da locomoção, ou especificamente para natação, o custo de nado. As diferenças no custo de nado entre os indivíduos parecem ser influenciadas por dois principais fatores, a resistência hidrodinâmica e habilidade técnica do nadador. O menor custo de nado apresentado pelas mulheres tem sido atribuído a menor resistência hidrodinâmica decorrente de menor tamanho corporal, maior percentagem de gordura e melhor posicionamento horizontal. Porém, essas diferenças no custo de nado entre homens e mulheres desaparecem quando corrigidos para o tamanho corporal. Em relação às crianças, o maior custo de nado comparado com o dos adultos quando corrigidos para o tamanho corporal pode ser explicado principalmente por menor habilidade técnica apresentada por elas. Para indivíduos com as mesmas características antropométricas, melhor habilidade técnica e maior tamanho da superfície de propulsão, associados a aumento na eficiência propulsiva, podem reduzir o custo de nado. Quando se comparam os diferentes estilos, o mais econômico é o crawl seguido pelo de costas em qualquer velocidade de nado. O borboleta é o estilo menos econômico a baixas velocidades (< 0,8m·s¹). Entretanto, acima dessa velocidade o peito passa a ser o estilo menos econômico.<br>La cantidad de energía metabólica gastada en transportar la masa corporal de un individuo por unidad de distancia ha sido definida como el desgaste energético de locomoción, o específicamente para la natación, el desgaste de nado. Las diferencias en el desgaste de nado entre los individuos parecen ser influenciadas por dos principales factores, la resistencia hidrodinámica y la habilidad técnica del nadador. El menor desgaste de nado presentado por las mujeres ha sido atribuido a una menor resistencia hidrodinámica proveniente de un menor tamaño corporal, mayor porcentaje de grasa, y mejor posicionamiento horizontal. Sin embargo, estas diferencias en el desgaste de nado entre hombres y mujeres desaparece cuando se corrige el tamaño corporal. En relación a los niños, el mayor desgaste de nado comparado a los adultos cuando se corrige el tamaño corporal puede ser explicado principalmente por una menor habilidad técnica presentada por los mismos. Para individuos con las mismas características antropométricas, una mejor habilidad técnica y mayor tamaño de superficie de propulsión, asociados a un aumento en la eficacia de propulsión, pueden reducir el desgaste de nado. Cuando se comparan los diferentes estilos, el más económico es el de pecho seguido por el de espalda a cualquier velocidad de nado. El estilo mariposa es el estilo menos económico a bajas velocidades (< 0,8 m·s-1). A pesar de esto, por encima de esta velocidad el estilo pecho pasa a ser el estilo menos económico.<br>The amount of metabolic energy spent in transporting the body mass of the subject over a unit of distance has been defined as the energy cost of locomotion, or regarding to swimming, cost of swimming. The differences in the cost of swimming between the individuals seem to be influenced by two main factors, the hydrodynamic resistance and technical skill of the swimmer. The lower cost of swimming showed by females has been attributed to a smaller hydrodynamic resistance due to their smaller size, larger percentage fat and more streamlined position. However, the difference in cost of swimming between males and females disappears when correcting for body size. With regard to children, the higher energy cost of swimming when correcting for body size may be caused by the lower swimming technique showed by them. For individuals with the same anthropometric characteristics, the better swimming technique and larger size of propelling surface, associated with higher propelling efficiency, may decrease the energy cost of swimming. When comparing different types of strokes, the most economical stroke is crawl, followed by backstroke, irrespective the swimming velocity. Butterfly is the less economical at low velocities (< 0.8 m·s¹). However, above that velocity the breaststroke become the less economical stroke