Global phosphoproteomic profiling of skeletal muscle in ovarian hormone-deficient female mice

Dynapenia, the age-related loss of skeletal muscle strength without the loss of muscle mass, significantly impacts the activities and quality of life of the aging population. Studies have shown that dynapenia occurs earlier in females than males in both human and rodent studies. Moreover, in females, estrogen deficiency has been shown to contribute to the loss of skeletal muscle strength as well as blunted recovery of strength after injury. The maintenance of skeletal muscle contractile function is vital to the overall health of women, especially as women live 1/3 of their life in an estrogen deficient state. Reversible protein phosphorylation is an indispensable post-translational modification, playing a key role in signal transduction pathways. Phosphorylation of skeletal muscle proteins have been shown to regulate sarcomeric function, excitation-contraction coupling, energy metabolism, and fiber-type composition. To define the physiological changes in the skeletal muscle phosphoproteome associated with estrogen deficiency, we used an ovariectomy model coupled with mass spectrometry. We identified, in total, 5,424 unique phosphorylation sites and 1,177 phosphoproteins in the tibialis anterior muscle. Ingenuity Pathway Analysis show decreased phosphorylation of contractile proteins and significant predicted inhibition of the upstream kinase, CDK6 (z-score -2.0) in ovariectomized compared to control muscles. Our results suggest that estrogen deficiency remodels the skeletal muscle phosphoproteome which may alter phosphorylation signaling that might contribute to the loss of strength in females.

Population Genetic Polymorphism of Skeletal Muscle Strength Related Genes in Five Ethnic Minorities in North China

Musculoskeletal performance is a complex trait influenced by environmental and genetic factors, and it has different manifestations in different populations. Heilongjiang province, located in northern China, is a multi-ethnic region with human cultures dating back to the Paleolithic Age. The Daur, Hezhen, Ewenki, Mongolian and Manchu ethnic groups in Heilongjiang province may have strong physical fitness to a certain extent. Based on the genetic characteristics of significant correlation between some important genes and skeletal muscle function, this study selected 23 SNPs of skeletal muscle strength-related genes and analyzed the distribution of these loci and genetic diversity in the five ethnic groups. Use Haploview (version 4.1) software to calculate the chi-square and the Hardy-Weinberg equilibrium to assess the difference between the two ethnic groups. Use R (version 4.0.2) software to perform principal component analysis of different ethnic groups. Use MEGA (version 7.0) software to construct the phylogenetic tree of different ethnic groups. Use POPGENE (version 1.32) software to calculate the heterozygosity and the FST values of 23 SNPs. Use Arlequin (version 3.5.2.2) software to analyze molecular variance (AMOVA) among 31 populations. The results showed that there was haplotype diversity of VDR, angiotensin-converting enzyme, ACTN3, EPO and IGF1 genes in the five ethnic groups, and there were genetic differences in the distribution of these genes in the five ethnic groups. Among them, the average gene heterozygosity (AVE_HET) of the 23 SNPs in the five populations was 0.398. The FST values of the 23 SNPs among the five ethnic groups varied from 0.0011 to 0.0137. According to the principal component analysis, the genetic distance of Daur, Mongolian and Ewenki is relatively close. According to the phylogenetic tree, the five ethnic groups are clustered together with the Asian population. These data will enrich existing genetic information of ethnic minorities.

Behavioral and Neurochemical Shifts at the Hippocampus and Frontal Cortex Are Associated to Peripheral Inflammation in Balb/c Mice Infected with Brucella abortus 2308

Brucellosis is a zoonosis affecting 50,000,000 people annually. Most patients progress to a chronic phase of the disease in which neuropsychiatric symptoms upsurge. The biological processes underlying the progression of these symptoms are yet unclear. Peripheral inflammation mounted against Brucella may condition neurochemical shifts and hence unchained neuropsychiatric disorders. Our work aimed at establishing whether neurological, behavioral, and neurochemical disarrays are circumstantially linked to peripheral inflammation uprise secondary to Brucella abortus 2308 infections. We then evaluated, in control and Brucella-infected mice, skeletal muscle strength, movement coordination, and balance and motivation, as well as dopamine, epinephrine, norepinephrine, and serotonin availability in the cerebellum, frontal cortex, and hippocampus. Serum levels of proinflammatory cytokines and corticosterone in vehicle-injected and -infected mice were also estimated. All estimates were gathered at the infection acute and chronic phases. Our results showed that infected mice displayed motor disabilities, muscular weakness, and reduced motivation correlated with neurochemical and peripheral immunological disturbances that tended to decrease after 21 days of infection. The present observations support that disturbed peripheral inflammation and the related neurochemical disruption might lead to mood disorders in infected mice. Future experiments must be aimed at establishing causal links and to explore whether similar concepts might explain neurological and mood disorders in humans affected by brucellosis.

ADAPTAÇÕES DO MÚSCULO ESQUELÉTICO AO ENVELHECIMENTO E AO TREINAMENTO: UMA REVISÃO NARRATIVA SOBRE A SARCOPENIA E A DINAPENIA

O crescimento da população idosa ressalta a importância da investigação sobre os efeitos do envelhecimento no sistema musculoesquelético. O objetivo desse estudo foi discutir sobre a terminologia da sarcopenia e da dinapenia, bem como revisar as adaptações do músculo esquelético ao envelhecimento e ao treinamento de força. A busca eletrônica foi conduzida nas bases de dados MEDLINE e Scopus em março de 2016 utilizando-se os termos aging, skeletal muscle, strength e dynapenia. O declínio da capacidade de produção de força muscular em decorrência do envelhecimento recebeu a denominação científico-clínica de Dinapenia. Apesar disto, ainda existe uma gama de pesquisadores que utiliza esta definição como parte do construto de Sarcopenia. Fatores neurais e fatores musculares constituem os mecanismos que contribuem para a instalação da dinapenia. Os fatores neurais englobam alterações no recrutamento e na sincronização de unidades motoras, a queda taxa de disparo e na velocidade de condução nervosa, a denervação das fibras musculares tipo II (rápidas) por morte neuronal e reinervação das fibras tipo I (lentas). Os fatores musculares são constituídos por alterações na arquitetura muscular, mudanças de tipo de fibra, disfunções no processo de acoplamento excitação-contração, alterações estruturais na miosina e infiltrações de lipídios intra e intermusculares. A dinapenia é diagnosticada baseada em uma avaliação dos fatores de risco, do teste de força de extensão de joelhos ou preensão manual. A partir do entendimento dos diversos mecanismos que contribuem para a instalação da dinapenia, pesquisadores das ciências da saúde podem ter embasamento para uma melhor prescrição de tratamentos preventivos ou mesmo de reabilitação da dinapenia.