Biology subjects

Pamplona, R.

Publications and source records attributed to Pamplona, R..

6 recordsLinked to original sources

bioRxiv2025

Non-linear and time-domain sleep qEEG features predict CSF protein damage markers in early Alzheimers disease

Study ObjectivesIn preclinical Alzheimers disease (AD), oxidative stress plays a key role in the pathogenesis by promoting non-enzymatic protein modifications that lead to the accumulation of oxidized species, established biomarkers of oxidative damage detectable in cerebrospinal fluid (CSF). These molecular alterations contribute to impaired proteostasis and the dysfunction of sleep-regulating neural circuits, resulting in altered sleep electroencephalographic patterns. Due to the invasiveness of CSF sampling, quantitative electroencephalography (qEEG) is proposed as a non-invasive alternative for assessing oxidatively modified protein levels via Machine Learning (ML). MethodsForty-two mild-to-moderate AD patients underwent polysomnography (PSG). QEEG features were extracted. CSF protein oxidation markers levels --glutamic semialdehyde, aminoadipic semialdehyde, N{varepsilon}-carboxyethyl-lysine, N{varepsilon}-carboxymethyl-lysine, and N{varepsilon}-malondialdehyde-lysine --were assessed by gas chromatography/mass spectrometry, and ML models trained to predict CSF biomarker levels. Model generalizability was validated using EEG data from healthy controls. ResultsqEEG features from slow-wave sleep (SWS) and rapid eye movement (REM) sleep, particularly over frontal and central regions, yielded R2 > 0.625 for patients biomarker prediction. ConclusionqEEG is a non-invasive, scalable tool for detecting AD-related oxidative processes, with potential implications for early diagnosis and risk stratification. HighlightsO_LISleep EEG features predict CSF oxidative biomarkers in early Alzheimers disease. C_LIO_LIPeak-to-peak amplitude, variance, and entropy were the top predictive features. C_LIO_LINREM sleep, especially SWS, and REM sleep provided the most informative EEG signals. C_LIO_LIEEG-based models achieved accurate, non-invasive biomarker estimation. C_LIO_LISleep qEEG may enable early detection and risk stratification in Alzheimers. C_LI

neuroscience↗

bioRxiv2023

Remote ischemic conditioning modulates inflammatory response and metabolic pathways

Remote ischemic conditioning (RIC) is an endogenous procedure that reduces ischemic injury by repeated transient mechanical obstruction of vessels at a remote limb. However, the specific mechanism of this protective phenomenon remains incompletely understood. We aimed to study perturbations in the brain and plasma metabolome following RIC as well as to identify potential novel inflammatory cytoprotective targets. A mouse model of transient focal cerebral ischemia by compressing the distal middle cerebral artery was used. Multiplex cytokine assay was performed in plasma samples. Blood plasma and brain samples were collected and metabolomes analyzed using non-targeted LC-MS. The analysis revealed a moderate impact on the brain metabolome compared to circulatory metabolites following RIC intervention. Interestingly, 3 plasma metabolites, Cer(42:3), HexCer(36:1) and TG(28:0), stood out as highly significantly upregulated. Moreover, RIC applied during the ischemia (RIPerC) and after the ischemia (RIPostC) protect against cerebral ischemia-reperfusion injury by modulating the peripheral immunomodulation. This study indicated that RIC neuroprotection is present in ischemic mice via the inflammatory response and metabolic changes both in the peripheral blood and ischemic brain.

neuroscience↗

bioRxiv2022

Lipidomic alterations in the cerebral cortex and white matter in sporadic Alzheimer's disease

AimsNon-targeted lipidomics analysis was conducted in post-mortem human frontal cortex area 8 (GM) and white matter of the frontal lobe centrum semi-ovale (WM) to identify lipidomes in middle-aged individuals with no neurofibrillary tangles and senile plaques, and cases at progressive stages of sporadic Alzheimers disease (sAD). MethodsLipidomic analysis using an LC-MS/MS platform was carried out in selected cases with suitable post-mortem lacking co-morbidities and concomitant brain pathologies. Complementary data were obtained using RT-qPCR and immunohistochemistry. ResultsThe WM shows an adaptive lipid phenotype resistant to lipid peroxidation, characterized by a lower fatty acid unsaturation, peroxidizability index, and higher ether lipid content than the GM. Changes in the lipidomic profile more marked in the WM than in GM occur in AD with disease progression. WM alterations are characterized by a decline in the content of branched fatty acid esters of hydroxy fatty acids (FAHFA), diacylglycerols (DG), triacylglycerols (TG), glycerophospholipids (GP) (especially ether lipids), and sphingolipids (especially sulfatides, ceramides, and glycosphingolipids). The GM acquires a fatty acid profile prone to peroxidation in sAD, while WM reinforces its peroxidation-resistant trait. Transcriptomic data point to additional defects of peroxisomal function. ConclusionsFour functional categories are associated with the different lipid classes affected in sAD: membrane structural composition, bioenergetics, antioxidant protection, and bioactive lipids, with deleterious consequences affecting both neurons and glial cells favoring disease progression.

neuroscience↗

bioRxiv2021

The effect of external stimulation on functional networks in the aging healthy human brain

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve as a more specific biomarker relating local activity with global brain dynamics. Here, we used a large resting-state fMRI dataset divided into middle-aged (N=310, aged < 65 years) and older adults (N=310, aged[≥] 65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space, each with a probabilistic occurrence and frequency. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations with different intensities in each node to force transitions from the brain states of the older group to the middle-age group. We found that the precuneus, a brain area belonging to the default mode network and the rich club, was the best stimulation target. These findings might have important implications for designing neurostimulation interventions to revert the effects of aging on whole-brain dynamics.

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bioRxiv2020

Whole-brain dynamics in aging: disruptions in functional connectivity and the role of the rich club

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups ( middle-age group (n=310); age range, 50-65 years vs. older group (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

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bioRxiv2019

Nuclear lipidome is altered in amyotrophic lateral sclerosis: a preliminary study

In this pilot study, we show that nuclei in spinal cord from ALS patients exhibit a differential lipidomic signature. Among the differential lipid species we could annotate 41 potential identities. These comprise membrane-bound lipids such as phosphatidylethanolamines-including plasmalogens- and phosphatidylcholines but also other lipid classes such as glycosphingolipids, diacylglycerols, and triacylglycerides (potentially present as nuclear lipid droplets). These results were orthogonally validated by showing loss of alkyldihydroxyacetonephosphate synthase (AGPS), a key peroxisomal enzyme in plasmalogen synthesis, both in ALS necropsy samples, in human motor neurons derived from iPSC from ALS patients and in hSOD-G93A transgenic mice. Further, diacylglycerol content changes were associated to ALS-linked variations in related-enzymes, such as phospholipase C {beta}I (PLC{beta}I), the source of nuclear diacylglycerol, and protein kinase C{beta}II (PKC{beta}II), whose function partially depends on nuclei concentration of diacylglycerol. These results point out for not only a role of nuclear membrane lipids but also to lipids present in the nucleoplasm, suggesting an undisclosed role for this part of the subcellular lipidome in ALS pathophysiology.

neuroscience↗