Publicaciones: diciembre 2022

Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective of Chronological Age

Jiménez-Balado J, Giralt-Steinhauer E, Fernández-Pérez I, Rey L et al. Biology (Basel). 2022 Dec 24;12(1):33. doi: 10.3390/biology12010033. PMID: 36671726; PMCID: PMC9855342.

https://pubmed.ncbi.nlm.nih.gov/36671726/

Abstract: In this manuscript we studied the relationship between WMH and biological age (B-age)in patients with acute stroke. We included in this study 247 patients with acute stroke recruited at Hospital del Mar having both epigenetic (DNA methylation) and magnetic resonance imaging data. WMH were measured using a semi-automated method. B-age was calculated using two widely used methods: the Hannum and Horvath formulas. We used multiple linear regression models to interrogate the role of B-age on WMH volume after adjusting for chronological age (C-age) and other covariables. Average C-age of the sample was 68.4 (±11.8) and we observed a relatively high median WMH volume (median = 8.8 cm3 , Q1–Q3 = 4.05–18.8). After adjusting for potential confounders, we observed a significant effect of B-ageHannum on WMH volume (βHannum = 0.023, p-value = 0.029) independently of C-age, which remained significant (βC-age = 0.021, p-value = 0.036). Finally, we performed a mediation analysis, which allowed us to discover that 42.7% of the effect of C-age on WMH is mediated by B-ageHannum. On the other hand, B-ageHoarvath showed no significant associations with WMH after being adjusted for C-age. In conclusion, we show for the first time that biological age, measured through DNA methylation, contributes substantially to explain WMH volumetric burden irrespective of chronological age.

Funding: This work was supported by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III with the grants “Registro BASICMAR” Funding for Research in Health (PI051737), “GWALA project” from Fondos de Investigación Sanitaria ISC III (PI10/02064), (PI12/01238), (PI15/00451), (PI18/00022), (PI21/00593); Fondos FEDER/EDRF Spanish stroke research network INVICTUS+ (RD16/0019/0002) and Grant “RICORS-ICTUS” (RD21/0006/0021) funded by Instituto de Salud Carlos III (ISCIII) and by the European Union NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). Additional support provided by Recercaixa’13 (JJ086116). E.G.-S. received a Juan Rodés research contract (JR18/00004—Spain’s Ministry of Health-Instituto de Salud Carlos III).

High prevalence of non-alcoholic fatty liver disease in patients with a first episode of acute ischemic stroke. Impact on disability and death

Lidia Canillas; Agnes Soriano Varela; Ana Rodríguez-Campello; Eva Giralt-Steinhauer; Elisa Cuadrado-Godia; Teresa Broqueta. Front Endocrinol. 2022 Dec 16;13:1003878.. doi: 10.3389/fendo.2022.1003878. eCollection 2022.

https://pubmed.ncbi.nlm.nih.gov/36589812/

Conclusion: Presence of NAFLD did not impact on disability and death after the stroke. However, patients with a first episode of stroke showed a high prevalence of NAFLD, especially at intermediate ages, and therefore, screening for NAFLD should be advisable.

Funding: Supported in part by “RICORS-ICTUS RD21/0006/0021)”grant, funded by Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union.

Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance

Cabral-Costa JV, Vicente-Gutiérrez C, Agulla J, Lapresa R, Elrod JW, Almeida Á, Bolaños JP, Kowaltowski AJ. J Neurochem. 2022 Dec 23. doi: 10.1111/jnc.15745. Online ahead of print. PMID: 36563047
Abstract: Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mito c ho nd r ia l c a lc ium unip o rte r c o mp le x (M C Uc ), while e fflu x occurs ma in ly through the mito c ho nd r ia l Na+/Ca2+ exchanger (N C LX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared to neurons. To assess the role of NCLX in mo us e p rima ry c ulture astrocytes, we inhib ited its functio n both pharmacologically or genetically. This re s ulte d in re -shaping of c yto s o lic C a2+ signa ling and a me ta b o lic s hift that increased glycolyt ic flux and lactate secretion in a C a2+-dependent manner. Interestingly, in v iv o genetic deletion of N CLX in hippocampal astrocytes improved cognit ive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX imp a ire d cognitive performance. These results unveil a role for N CLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition.
Funding: Authors were supported by grant #2020/06970–5 from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Centro de Pesquisa, Inovação e Difusão de Processos Redox em Biomedicina (CEPID Redoxoma, FAPESP grant #2013/07937–8); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) line 001; Agencia Estatal de Investigación (PID2019-105699RB-I00/AEI/10.13039/501100011033, PDC2021-121013-I00 and RED2018‐102576‐T to JPB); Plan Nacional de Drogas (2020I028 to JPB); Instituto de Salud Carlos III (PI21/00727 and RD21/0006/0005 co-funded by the European Union FEDER/FSE+ and NextGenerationEU to AA); and Junta de Castilla y León(CS/151P20 co-funded by P.O. FEDER to AA; Apoyo Regional a la Competitividad Empresarial, ICE 04/18/LE/0017 to JPB, and Escalera de Excelencia CLU-2017-03 to JPB and AA). JVCC was also supported by FAPESP fellowships #2017/14713-0 and #2019/22178-2.

Association of blood-based biomarkers with radiologic markers and cognitive decline in atrial fibrillation patients

Palà E, Escudero-Martínez I, Penalba A, Bustamante A, Lamana-Vallverdú M et al. J Stroke Cerebrovasc Dis. 2022 Dec;31(12):106833. doi: 10.1016/j.jstrokecerebrovasdis.2022.106833. Epub 2022 Oct 26.PMID: 36309005
Background: Atrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk. Methods: The present study followed a cross-sectional design. 70 patients with a history of AF and CHADS2 score 1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain
MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany. Results: 45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to
be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.9923.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment. Conclusions: BMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.
Funding: A Junta de Andalucía grant (PIN-0144-2016) supported partially the study. The Fundacion Cajasol contributed to the study. Neurovascular Research Groups at Seville and Barcelona are part of the Spanish Neurovascular Disease Research Network (RICORS-ICTUS, RD21/0006/0007).