Publicaciones: marzo 2023

Cross-talk between energy and redox metabolism in astrocyte-neuron functional cooperation

Almeida A, Jimenez-Blasco D, Bolaños JP. Essays Biochem. 2023 Mar 3;67(1):17-26. doi: 10.1042/EBC20220075. PMID: 36805653

https://pubmed.ncbi.nlm.nih.gov/36805653/

Abstract: Astrocytes show unique anatomical, morphological, and metabolic features to take up substrates from the blood and metabolize them for local delivery to active synapses to sustain neuron function. In the present review, we specifically focus on key molecular aspects of energy and redox metabolism that facilitate this astrocyte-neuronal coupling in a controlled manner. Basal glycolysis is co-ordinated by the anaphase-promoting complex/cyclosome (APC/C)-Cdh1, a ubiquitin ligase that targets the proglycolytic enzyme 6-phosphofructokinase-2,6-bisphosphastate-3 (PFKFB3) for degradation. APC/C-Cdh1 activity is more robust in neurons than in astrocytes, which determine that PFKFB3 abundance and glycolytic rate are weaker in neurons. The low PFKFB3 activity in neurons facilitates glucose-6-phosphate oxidation via the pentose-phosphate pathway, which promotes antioxidant protection. Conversely, the high PFKFB3 activity in astrocytes allows the production and release of glycolytic lactate, which is taken up by neurons that use it as an oxidizable substrate. Importantly, the mitochondrial respiratory chain is tighter assembled in neurons than in astrocytes, thus the bioenergetic efficiency of mitochondria is higher in neurons. Because of this, the production of reactive oxygen species (mROS) by mitochondrial complex I is very low in neurons and very high in astrocytes. Such a naturally occurring high abundance of mROS in astrocytes physiologically determines a specific transcriptional fingerprint that contributes to sustaining cognitive performance. We conclude that the energy and redoxmetabolism of astrocytes must complementarily match that of neurons to regulate brain function and animal welfare.

Funding: This work was supported by the Agencia Estatal de Investigacion [grant numbers ´ PID2019-105699RB-I00/AEI/10.13039/501100011033, PDC2021-121013-I00, RED2018-102576-T (to J.P.B.)]; Plan Nacional de Drogas [grant number 2020I028 (to J.P.B.)]; Instituto de Salud Carlos III [grant numbers PI21/00727, RD21/0006/0005
cofunded by the European Union (to A.A.)]; and Junta de Castilla y Leon [grant number CS/151P20 cofunded by P.O. FEDER (to ´ A.A.)]; Apoyo Regional a la Competitividad Empresarial, [grant number ICE 04/18/LE/0017 (to J.P.B.)]; and Escalera de Excelencia [grant number CLU-2017-03 (to J.P.B. and A.A.)]. D.J.B. is a recipient of a Juan de la Cierva-Incorporacion contract [grant number ´ IJC2020-044230-I].

N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated with Post-Stroke In-Hospital Complications

Ruiz-Franco ML, Guevara-Sánchez E, Amaya-Pascasio L et al. J Pers Med. 2023 Mar 5;13(3):474. doi: 10.3390/jpm13030474. PMID: 36983656

https://pubmed.ncbi.nlm.nih.gov/36983656/

Abstract: Previous studies have shown the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) with stroke mortality and functional outcome after an acute ischemic stroke (AIS). Knowledge of its association with systemic and neurological in-hospital complications is scarce. Our objective is to analyze this. We performed an observational, retrospective study that included consecutive AIS patients during a 1-year period (2020). A multivariate analysis was performed to identify if NT-proBNP levels were independently associated with in-hospital complications. 308 patients were included, of whom 96 (31.1%) developed systemic and 62 (20.12%) neurological in-hospital complications. Patients with any complication (39.3%) showed higher NT-proBNP levels than those without (median (IQR): 864 (2556) vs. 142 (623) pg/dL, p < 0.001). The receiver operating characteristic curve (ROC) pointed to 326 pg/dL of NT-proBNP as the optimal cutoff level for developing in-hospital systemic complications (63.6% sensitivity and 64.7% specificity for any complication; 66.7% and 62.7% for systemic; and 62.9% and 57.7% for neurological complications). Multivariate analyses showed that NT-proBNP > 326 pg/dL was associated with systemic complications (OR 2.336, 95% CI: 1.259–4.335), adjusted for confounders. This did not reach statistical significance for neurological complications. NT-proBNP could be a predictor of in-hospital systemic complications in AIS patients. Further studies are needed.

Funding: This study is part of the Spanish Health Outcomes-Oriented Cooperative Research Networks (RICORTS-ICTUS), Instituto de Salud Carlos III (Carlos III Health Institute), Ministerio de Ciencia e Innovación (Ministry of Science and Innovation), RD21/0006/0010.

Treatment of Vascular Parkinsonism: A Systematic Review

Del Toro-Pérez C, Guevara-Sánchez E, Martínez-Sánchez P. Brain Sci. 2023 Mar 14;13(3):489. doi: 10.3390/brainsci13030489.PMID: 36979299

https://pubmed.ncbi.nlm.nih.gov/36979299/

Abstract: Background and aims: Although the distinction between vascular parkinsonism (VP) and idiopathic Parkinson’s disease (IPD) is widely described, it is not uncommon to find parkinsonisms with overlapping clinical and neuroimaging features even in response to levodopa treatment. In addition, several treatments have been described as possible adjuvants in VP. This study aims to update and analyze the different treatments and their efficacy in VP. Methods: A literature search was performed in PubMed, Scopus and Web of Science for studies published in the last 15 years until April 2022. A systematic review was performed. No meta-analysis was performed as no new studies on response to levodopa in VP were found since the last systematic review and meta-analysis in 2017, and insufficient studies on other treatments were located to conduct it in another treatment subgroup. Results: Databases and other sources yielded 59 publications after eliminating duplicates, and a total of 12 original studies were finally included in the systematic review. The treatments evaluated included levodopa, vitamin D, repetitive transcranial magnetic stimulation (rTMS) and intracerebral transcatheter laser photobiomodulation therapy (PBMT). The response to levodopa was lower in patients with VP with respect to IPD. Despite this, there has been described a subgroup of patients with good response, it being possible to identify them by means of neuroimaging techniques and the olfactory identification test. Other therapies showed encouraging results in studies with some risk of bias. Conclusions: The response of VP to different therapeutic strategies is modest. However, there is evidence that a subgroup of patients can be identified as more responsive to L-dopa based on clinical and neuroimaging criteria. This subgroup should be treated with L-dopa at appropriate doses. New therapies such as vitamin D, rTMS and PBMT warrant further studies to demonstrate their efficacy.

Funding: This study is part of the Spanish Health Outcomes-Oriented Cooperative Research Networks (RICORS-ICTUS), Instituto de Salud Carlos III (Carlos III Health Institute), Ministerio de Ciencia e Innovación (Ministry of Science and Innovation), RD21/0006/0010.