Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNA7 mouse model of SMA

Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in reduced levels of the SMN protein and the selective degeneration of lower MNs. The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in SMA leads to widespread splicing abnormalities. We used the SMN?7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules (PARGs) enriched in the splicing regulator Sam68. However, these granules lacked other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which are essential for mRNA processing and nuclear export. These effects were accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x and Nrnx1 genes, as well as changes in the relative accumulation of the intron-containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN functions. PARG-containing MNs were observed at presymptomatic SMA stage, increasing their number during the symptomatic stage. Moreover, the massive accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic depletion of polyadenylated mRNAs for their translation. We suggest that the SMN-dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs reflects a severe dysfunction of both mRNA processing and translation, which could contribute to SMA pathogenesis.This work was supported by grants from: “Dirección General de Investigación” of Spain (BFU2014-54754-P and SAF2015-70801-R, cofinanced by FEDER) and “Instituto de Investigación Marqués de Valdecilla-IDIVAL (NVAL17/22). Dr. Tapia is the recipient of a grant from SMA Europe and FundAME (Spain)

Perfil da condição bucal de idosas do Distrito Federal Oral health status of elderly women from the Brazilian Federal District

Os trabalhos realizados no Brasil a respeito das principais afecções bucais dos gerontes mostram situação preocupante. O objetivo deste estudo foi estimar a frequência de edentulismo, analisar o uso e a necessidade de prótese, calcular o índice CPOD e verificar a condição periodontal de idosas residentes no Distrito Federal. Cento e quarenta mulheres com idade igual ou superior a sessenta anos foram examinadas. A condição de cada prótese foi avaliada observando presença de prejuí­zo estético ou funcional. Em seguida, foi realizado exame clínico para detectar a presença de cárie, restaurações e dentes perdidos para cálculo do índice CPOD. O exame periodontal incluiu a verificação do índice de placa visível, índice de sangramento gengival, medidas de profundidade de sondagem clínica, perda de inserção clínica e mobilidade dental de todos os dentes presentes. Os resultados revelaram péssimas condições bucais dos pacientes examinados. A taxa de edentulismo mostrou-se elevada, o índice CPOD foi alto (29,8), com predomínio do componente extraído (87,1%) e a condição periodontal foi considerada grave. A partir destes dados, pode-se concluir que o perfil da condição bucal das idosas representadas neste estudo é precário, o que reflete a necessidade de se elaborar programas de promoção de saúde e de reabilitação para este segmento da população.<br>Data from Brazilian researches that evaluated oral health of elderly people show a worrisome situation. The purpose of this study was to estimate the frequency of edentulism, analyze both the use and need profiles of prosthesis, calculate the DMFT index and check the condition of periodontal elderly residents in the Federal District. One hundred and forty women aged 60 years or above were examined. The condition of each prosthesis was evaluated to detect the presence of functional or aesthetic damage. Then, clinical examination was carried out to detect the number of decayed, missing or filled teeth in order to calculate the DMFT index. The periodontal examination included the index of visible plaque, bleeding index, measurement of clinical probing depth, measurement of clinical attachment level and teeth mobility. The results showed poor oral conditions of the patients. The rate of edentulism was high, the DMFT index was elevated (29.8) with a predominance of the extracted component (87.1%) and periodontal condition was considered severe. From these data we can conclude that the oral condition of elderly represented in this study is precarious and reflects the need for health promotion and rehabilitation programs for this segment of the population