Publicaciones

Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice

Fraga E, Medina V, Cuartero MI et al. Front Cell Neurosci. 2023 Aug 11;17:1219847. doi: 10.3389/fncel.2023.1219847. eCollection 2023. PMID: 37636586

https://pubmed.ncbi.nlm.nih.gov/37636586/

Abstract: Chronic cerebral hypoperfusion due to carotid artery stenosis is a major cause of vascular cognitive impairment and dementia (VCID). Bilateral carotid artery stenosis (BCAS) in rodents is a well-established model of VCID where most studies have focused on white matter pathology and subsequent cognitive deficit. Therefore, our aim was to study the implication of adult hippocampal neurogenesis in hypoperfusion-induced VCID in mice, and its relationship with cognitive hippocampal deficits. Mice were subjected to BCAS; 1 and 3 months later, hippocampal memory and neurogenesis/cell death were assessed, respectively, by the novel object location (NOL) and spontaneous alternation performance (SAP) tests and by immunohistology. Hypoperfusion was assessed by arterial spin labeling-magnetic resonance imaging (ASL-MRI). Hypoperfused mice displayed spatial memory deficits with decreased NOL recognition index. Along with the cognitive deficit, a reduced number of newborn neurons and their aberrant morphology indicated a remarkable impairment of the hippocampal neurogenesis. Both increased cell death in the subgranular zone (SGZ) and reduced neuroblast proliferation rate may account for newborn neurons number reduction. Our data demonstrate quantitative and qualitative impairment of adult hippocampal neurogenesis disturbances associated with cerebral hypoperfusion-cognitive deficits in mice. These findings pave the way for novel diagnostic and therapeutic targets for VCID. 

Funding: This work was supported by grants from Spanish Ministry of Science and Innovation (MCIN) PID2019-106581RB-I00 (MM), from Leducq Foundation for Cardiovascular ResearchbTNE-19CVD01 (MM) and TNE-21CVD04 (MM and IL), and from Instituto de Salud Carlos III (ISCIII) and co-financed by the European Development Regional Fund “A Way to Achieve Europe” PI20/00535 and RICORS-ICTUS RD21/0006/0001 (IL). CNIC was supported by ISCIII, MCIN, and ProCNIC Foundation, and is a Severo Ochoa Center of Excellence
(CEX2020-001041-S). The microscopy experiments were performed in Unidad de Microscopía e Imagen Dinámica, CNIC, ICTS-ReDib, co-funded by MCIN/AEI/10.13039/501100011033 and FEDER “Una manera de hacer Europa” (#ICTS-2018- 04-CNIC-16). Part of the research work included in this publication has been carried out in the ReDIB ICTS infrastructure BioImaC, MCIN.

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes

Llucià-Carol L, Muiño E, Cullell N et al. Int J Mol Sci. 2023 Aug 30;24(17):13452. doi: 10.3390/ijms241713452. PMID: 37686257

https://pubmed.ncbi.nlm.nih.gov/37686257/

Abstract: We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10−2 , se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = −0.04, p-value = 1.3 × 10−3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10−4 , se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10−2 , se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.

Funding: This work was supported by the Spanish National Research Council (CSIC) via COVID19 Funds (Ref.CSIC202020E086), the European Commission—NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform, the Instituto de Salud Carlos III through the iBioStroke project (AC19/00106 Eranet-Neuron, European research grants), the RICORS RD21/0006/0006, FEDER, NextGeneration EU, the PREVICTUS project (PMP21/00165), and the COPYCTUS project (PI21/01088). IIB SANT PAU is funded by the Catalan Government (CERCA Program/ Generalitat de Catalunya). M.L. is funded by a PFIS Contract (Contratos Predoctorales de Formación en Investigación en Salud FI19/00309) from Instituto de Salud Carlos III (ISCIII). C.G.-F. is supported by a Sara Borrel contract (CD20/00043) from Instituto Carlos III and Fondo Europeo de Desarrollo Regional (ISCIII-FEDER). The BelCovid cohort is funded by The Belgian National Funds for Scientific Research and Fondation Léon Fredericq.