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Periche-Tomas, E.

Publications and source records attributed to Periche-Tomas, E..

2 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

Developing Interferon-β as a safe in-vivo experimental-medicine model of human inflammation.

BackgroundInflammation is increasingly implicated in a wide range of neuropsychiatric disorders ranging from depression through age- and infection-related cognitive decline to dementia. Arguably, the most important evidence supporting an aetiological role for inflammation in these conditions in humans has come from studies of patients receiving IFN- therapeutically or longitudinal follow-up of patients after naturalistic infections (e.g., hepatitis C). These experimental medicine-type approaches have identified a discrete set of brain regions e.g. amygdala-hippocampus-hypothalamus, insula and anterior cingulate as well as dopamine-rich subcortical structures that are particularly sensitive to systemic inflammation. Coupled with renewed interest in developing novel immune-targeted therapies for neuropsychiatric disorders as diverse as depression and neurodegenerative disorders, this has highlighted the urgent need for a safe, reliable in-vivo experimental medicine model of inflammation that can be used across the age range. To date, this need has been partially addressed by access to short-acting forms of Interferon-alpha or human (GMP) grade lipopolysaccharide (LPS). However, unpegylated IFN- is no longer commercially available and the costs and cardiovascular monitoring requirements of low-dose (i.e. 0.8-1ng/Kg i.v. endotoxin) LPS are prohibitive and particularly challenging to use in older or more vulnerable populations. AimDevelop a new experimental model of human inflammation that elicits robust sickness responses within a few hours but with minimal cardiovascular effects, thus avoiding the need for continuous cardiac monitoring and ensuring applicability across diverse experimental contexts and participant groups from the young to the elderly. MethodsUsing a randomized, placebo-controlled, repeated measures cross-over design, physiological, behavioural, immune and transcriptomic responses were collected from 30 healthy volunteers (15 young [18-34] and 15 old [60-75]) following both IFN-{beta} (EXTAVIA(R) [100 {micro}g]) and saline (placebo) injections. ResultsIFN-{beta} induced a robust systemic immune response, evidenced by significant increases in temperature, heart rate, immune cell activation (lymphocytes, monocytes and neutrophils) and levels of IFN-{beta}, IL-10 and TNF- cytokines. These physiological changes were accompanied by significant increases in negative mood, tiredness, tension and sickness symptoms aa well as by a decrease in vigour. ConclusionsFN-{beta} is a safe and robust new experimental model of mild acute inflammation, This minimally invasive and effective design can induce transient changes in systemic inflammation in healthy individuals from 18-75. A more refined, ecologically valid model similar to the mild inflammation typically reported in psychiatric disorders like depression or cognitive impairment.

immunology↗