Physical exercise shapes the mouse brain epigenome

[Objective]: To analyze the genome-wide epigenomic and transcriptomic changes induced by long term resistance or endurance training in the hippocampus of wild-type mice.[Methods]: We performed whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) of mice hippocampus after 4 weeks of specific training. In addition, we used a novel object recognition test before and after the intervention to determine whether the exercise led to an improvement in cognitive function.[Results]: Although the majority of DNA methylation changes identified in this study were training-model specific, most were associated with hypomethylation and were enriched in similar histone marks, chromatin states, and transcription factor biding sites. It is worth highlighting the significant association found between the loss of DNA methylation in Tet1 binding sites and gene expression changes, indicating the importance of these epigenomic changes in transcriptional regulation. However, endurance and resistance training activate different gene pathways, those being associated with neuroplasticity in the case of endurance exercise, and interferon response pathways in the case of resistance exercise, which also appears to be associated with improved learning and memory functions.[Conclusions]: Our results help both understand the molecular mechanisms by which different exercise models exert beneficial effects for brain health and provide new potential therapeutic targets for future research.This work was supported by the Spanish Association Against Cancer (PROYE18061FERN to M.F.F.), the Asturias Government (PCTI) co-funding 2018-2022/FEDER (IDI/2018/146 to M.F.F.), the Fundación General CSIC (0348_CIE_6_E to M.F.F.), the Health Institute Carlos III (Plan Nacional de I+D+I) co-funding FEDER (PI18/01527 to M.F.F and A.F.F.), the MINECO (DEP2015-69980-P to B.F.G.), and the Fundación Tatiana Pérez de Guzmán el Bueno (“Ayudas a Proyectos de Investigación en Neurociencia-2020” to C.T.Z and E.I.G.). R.G.U. is supported by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER). J.R.T. is supported by a Juan de la Cierva fellowship from the Spanish Ministry of Science and Innovation MCIN/AEI /10.13039/501100011033 (IJC2018-036825-I). R.F.P. is supported by the Severo Ochoa program (BP17-114). P.P.H. is supported by Ayudas para la realización de Tesis Doctorales. Modalidad A fellowship from the University of Oviedo (PAPI-20-PF-19). We also acknowledge support from the IUOPA-ISPA-FINBA (the IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain).Peer reviewe

Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients

11 pages, 6 figures.-- The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2334/9/186/pre pubBackground: Antigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein192-433, and the entire Trypanosoma rangeli HSP-70 protein. Methods: Seventeen Brazilian acute chagasic patients, 50 Colombian chronic chagasic patients (21 indeterminate and 29 cardiopathic patients) and 30 healthy individuals were included. Total IgG and its subtypes directed against the above-mentioned recombinant antigens were determined by ELISA tests. Results: The T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins were able to distinguish both acute from chronic chagasic patients and infected people from healthy individuals. Specific antibodies to T. cruzi crude antigen in acute patients came from IgG3 and IgG4 subclasses whereas IgG1 and IgG3 were the prevalent isotypes in indeterminate and chronic chagasic patients. By contrast, the specific prominent antibodies in all disease stages against T. cruzi KMP-11 and T. rangeli HSP-70 recombinant antigens were the IgG1 subclass.This work was supported by Colciencias Research project No. 1203-333- 18692. IDF was supported by Colciencias and the Universidad Javeriana's Young Researcher 2008 Programme (Bogotá, Colombia). MCT and MCL were supported by P06-CTS-02242 Grant from PAI (Junta de Andalucia) and RICET-RD06/0021-0014, Spain. MS received financial support from the Brazilian agency - CNPq.Peer reviewe

MicroRNAs circulantes como biomarcadores emergentes para la progresión de la enfermedad de Huntington

La enfermedad de Huntington (EH) es una enfermedad neurodegenerativa causada por la expansión del triplete CAG en el exón 1 del gen HTT, caracterizada por alteraciones psicológicas y motoras. Complementariamente, la EH presenta una desregulación metabólica que implica a los tejidos periféricos y centros neuronales. Ante la afectación sistémica, se hace necesaria la búsqueda de biomarcadores capaces de evaluar el grado de afectación central y periférica durante el curso de la enfermedad. En este contexto, los microRNAs (miRNAs) han emergido como un nuevo mecanismo para el control de la regulación génica y comunicación intercelular, siendo utilizados como biomarcadores de progresión en distintas patologías. En este estudio hemos analizado el perfil de miRNAs circulantes plasmáticos de seis pacientes, que muestran entre 40 y 45 repeticiones CAG, y cinco sujetos control sanos de edad semejante. Los resultados obtenidos mediante qRT-PCR muestran que 99 miRNAs circulantes se encuentran alterados en los pacientes sintomáticos de la EH. Muchos de estos miRNAs han sido detectados tejido cerebral de la EH, otras enfermedades neurodegenerativas y desordenes metabólicos. Asimismo, 25 de los 99 miRNAs presentan dianas génicas en las principales rutas celulares encargadas de coordinar el estado metabólico y alta expresión en los tejidos modificados en la progresión de la enfermedad, pudiendo participar funcionalmente en la desregulación de estas vías. Por tanto, estos 25 miRNAs (miR-126-3p, miR-128, miR-130a-3p, miR-145-5p, miR- 146a-5p, miR-152, miR-181b-5p, miR-181d, miR-195-5p, miR-199a-5p, miR-21-5p, miR-214-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-23b-3p, miR-26a-5p, miR-27a-3p, miR-27b-3p, miR-301a-3p, miR-30d-5p, miR-335-5p, miR-584-5p, miR-941 y miR-99b-5p) presentan un alto potencial como marcadores biológicos de la fase sintomática de la EH