Biology subjects

Ronen, I.

Publications and source records attributed to Ronen, I..

3 recordsLinked to original sources

bioRxiv2026

Age and IFN-β-induced changes in glial morphometry can be captured by in vivo diffusion-weighted magnetic resonance spectroscopy.

IntroductionNeuroinflammation is increasingly implicated in age-related cognitive decline, neurodegeneration and neuropsychiatric disorders. During systemic inflammation, microglia are rapidly activated, simultaneously changing their shape and releasing cytokines that perturb neuronal function. This change in glial morphology alters their intracellular diffusion properties and provides a potentially measurable signature of their activation state. Diffusion-weighted magnetic resonance spectroscopy (dMRS) shows promise in detecting these changes. Here, we combined IFN-{beta} challenge with dMRS to assess changes in metabolite diffusion in healthy young and older adults. We hypothesised that IFN-{beta} would increase diffusion of choline-containing compounds (tCho) but not N-acetylaspartate + N-acetylaspartylglutamate (tNAA), age would be associated with an increase in tCho diffusion and concentration, lower tNAA concentration and increased effects of IFN-{beta}. MethodsWe recruited 15 young (mean 25.2 {+/-} 5.1 years, 6 male) and 15 older (mean 62.6 {+/-} 4.1 years, 5 male) healthy volunteers, each tested twice, once after IFN-{beta} and once after placebo. Physiological and behavioural responses were recorded hourly, and blood samples taken at baseline, 4 and 6.5 hours post-injection. dMRS occurred at [~]4.5 hours at 3T, using a semi-LASER sequence with four diffusion weightings (b = 0 and 3 x 3500 s/mm{superscript 2}), in 4.5 cm3 VOIs in the left thalamus and corona radiata. Apparent Diffusion Coefficients (ADCs) of tCho, tNAA and creatine+phosphocreatine (tCr) were calculated from averaged spectra using custom MATLAB software. ResultsIFN-{beta} administration produced a significant increase in thalamic tCho diffusivity compared with placebo (t(28) = -2.15, p = 0.040), with no change in tNAA or tCr ADC, or tCho concentrations. IFN-{beta}-related increases in tCho ADC positively correlated with increases in circulating IL-6 (R{superscript 2} = 0.14, p = 0.040). Age-related effects were also evident during the placebo condition, with older participants showing lower thalamic tNAA diffusivity (t(27) = 2.86, p = 0.008), lower tNAA/tCr in both grey and white matter (grey: t(27) = 2.49, p = 0.023; white: t(27) = 2.94, p = 0.007), and higher white-matter tCho/tCr (t(27) = -2.23, p = 0.034). ConclusiondMRS detected IFN-{beta}-induced increases in thalamic tCho diffusivity corresponding with peripheral inflammation, supporting its sensitivity to acute inflammation-induced changes in glial morphology. Age-related differences in tNAA diffusion and concentrations further highlight metabolite-specific ageing effects. HighlightsO_LIdMRS detects increased thalamic total choline diffusivity following IFN-{beta}-induced inflammation. C_LIO_LIIFN-{beta}-related changes in total choline diffusivity are associated with peripheral IL-6 responses. C_LIO_LIAgeing is linked to reduced NAA diffusion and higher white-matter tCho/tCr C_LIO_LIdMRS is sensitive to inflammation- and age-related neurochemical changes in vivo. C_LI

immunology↗

bioRxiv2025

Metabolic Dysfunction Underlying Fatigue in Multiple Sclerosis: Elevated Lactate and Impaired Post-Exercise Creatine Response in the Anterior Cingulate Cortex

BackgroundMultiple Sclerosis (MS) is characterised by altered brain metabolism and increased chronic perceived fatigue. However, the relationship between brain metabolites, fatigue, and physical task effects in MS remains unclear. This study investigated brain metabolite concentrations (glutamate + glutamine (Glx), lactate, and total creatine (tCr)) in the anterior cingulate cortex (ACC), a region involved in interoceptive processing, before and after a physical task. MethodsTwenty-two people with MS (pwMS) and 22 controls underwent Magnetic Resonance Spectroscopy before and after fatiguing wrist extension tasks. Linear mixed models analysed group differences and exercise-induced metabolite changes. ResultsPwMS showed higher ACC lactate concentrations than controls at rest and post-exercise (F = 7.08, p = 0.011, 95% CI[0.033, 0.228]). No significant Glx differences were observed. A significant group x exercise interaction for tCr occurred (F = 4.63, p = 0.037, 95% CI[0.027, 0.581]), with tCr decreasing post-exercise in controls (t = 3.09, p = 0.02) but remaining stable in pwMS. Changes in lactate correlated moderately with perceived effort in pwMS (r = 0.51, p = 0.04). ConclusionsThis study provides novel evidence of metabolic differences in pwMS, characterised by elevated lactate and stable post-exercise tCr, suggesting altered energy metabolism potentially linked to mitochondrial dysfunction.

neuroscience↗

bioRxiv2023

A 7T interleaved fMRS and fMRI study on visual contrast dependency in the human brain.

IntroductionsFunctional magnetic resonance spectroscopy (fMRS) is a non-invasive technique for measuring dynamic changes in neurometabolites. While previous studies have observed concentration changes in metabolites during neural activation, the relationship between neurometabolite response and stimulus intensity and timing requires further investigation. To address this, we conducted an interleaved fMRS and functional magnetic resonance imaging (fMRI) experiment using a visual stimulus with varying contrast levels. MethodsA total of 20 datasets were acquired on a 7T MRI scanner. The visual task consisted of two STIM blocks (30s/20s ON/OFF, four minutes), with 10% or 100% contrast, interleaved with a four minutes REST block. A dynamic fitting approach was used for fMRS data analysis. For metabolite level changes, the STIM conditions were modeled in two different ways: either considering the full STIM block as active condition (full-block model) or only modeling the ON blocks as active condition (sub-block model). For linewidth changes due to the BOLD effect, STIM conditions were modeled using the sub-block model. ResultsFor both models, we observed significant increases in glutamate levels for both the 10% and 100% visual contrasts, but no significant difference between the contrasts. Decreases in aspartate, and glucose, and increases in total N-acetylaspartate and total creatine were also detected, although less consistently across both 10% and 100% visual contrasts. BOLD-driven linewidth decreases and fMRI-derived BOLD increases within the MRS voxel were observed at both 10% and 100% contrasts, with larger changes at 100% compared to 10% in the fMRI-derived BOLD only. We observed a non-linear relation between visual contrast, the BOLD response, and the glutamate response. ConclusionOur study highlights the potential of fMRS as a complementary technique to BOLD fMRI for investigating the complex interplay between visual contrast, neural activity, and neurometabolism. Future studies should further explore the temporal response profiles of different neurometabolites and refine the statistical models used for fMRS analysis.

neuroscience↗