Biology subjects

Lopez-Gil, X.

Publications and source records attributed to Lopez-Gil, X..

5 recordsLinked to original sources

bioRxiv2026

A harmonized phantom MRI quality control framework identifies sources of longitudinal and multi-site variability

The shift towards open science in preclinical research requires high-quality, comparable data adhering to FAIR principles, yet rigorous quality assurance (QA) and quality control (QC) frameworks remain less established in preclinical magnetic resonance imaging (MRI) than in clinical imaging. To address this limitation, a multicenter study was conducted across 21 international laboratories using standardized commercial liquid phantoms for mouse and rat MRI setups and a harmonized acquisition protocol. Data processing was centralized using AIDAqc, an automated pipeline extracting quantitative metrics including signal-to-noise ratio (SNR), temporal SNR (tSNR), ghost-to-signal ratio (GSR), and motion-equivalent temporal instability, combined with five complementary outlier-detection algorithms. The evaluated datasets encompassed magnetic field strengths from 3.0 to 16.4 T and heterogeneous coil and acquisition configurations. In mouse phantom data, SNR and tSNR were significantly lower at 3 T than at 7 and 9.4 T, whereas artifact-related metrics did not differ significantly between field-strength groups. In rat phantom data, differences between field strengths were less pronounced. At 7 T, substantial dataset-specific differences were observed in anatomical and functional quality metrics, also among datasets using the similar coil configuration. Multicenter reference values for frequently represented 7 T configurations were established, including SNR/tSNR of 48 {+/-} 3/48 {+/-} 1 dB for mouse surface-coil datasets and 49 {+/-} 3/44 {+/-} 4 dB for rat array-coil datasets. Longitudinal anatomical SNR showed generally low variability, whereas ghosting was more variable across time. Automated outlier detection additionally identified transient acquisition instabilities that were not always apparent by visual inspection. Together, these findings show that field strength and nominal coil configuration alone do not adequately characterize MRI performance and support standardized, longitudinal phantom-based QC combined with automated analysis as a practical approach for improving the reliability, transparency, and interoperability of multicenter preclinical MRI data.

bioengineering↗

bioRxiv2025

Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype

Anxiety and depression are common in Parkinsons disease (PD), affecting quality of life. Aggregates of -synuclein (-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human -Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with -Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.

neuroscience↗

bioRxiv2025

Pre-amyloid cognitive intervention preserves brain function in aged TgF344-AD rats, maintaining connectivity and enhancing plasticity in a sex-specific manner

BackgroundAlzheimers disease is characterized by progressive cognitive decline and neurodegeneration, with cognitive reserve playing a key role in mitigating disease impact. Cognitive stimulation has been suggested as a non-pharmacological approach to enhance cognitive reserve and delay cognitive deterioration, but its underlying mechanism remains to be fully understood. This study investigates the effects of pre-amyloid cognitive intervention on brain connectivity, memory, synaptic plasticity and neuroinflammation in aged TgF344-AD rats, considering sex-specific differences. MethodsMale and female TgF344-AD and wild-type rats were assigned to trained and untrained groups, with cognitive stimulation administered through repetitive delayed nonmatch-to-sample tasks. Longitudinal magnetic resonance imaging acquisitions assessed training-induced changes in whole-brain functional connectomics and in particular entorhinal cortex connectivity. Memory was evaluated using the novel object recognition test. Cellular analysis of neurons (NeuN+, Parvalbumin+) and microglial cells, as well as molecular (PSD95, TrkB, p-RPS6, and VGLUT) analyses were conducted to determine the role of cognitive stimulation in modulating neuronal density, neuroinflammation and neuroplasticity. ResultsMale TgF344-AD rats undergoing prolonged cognitive stimulation had preserved global functional connectivity and exhibited improved recognition memory, compared to untrained animals, while TgF344-AD females did not follow this pattern. Entorhinal cortex connectivity was significantly loss in 19-month-old rats compared to wild-type rats and this was completely prevented by training. At a cellular level, cognitive stimulation significantly decreased the number of PV+ neurons in the dentate gyrus of trained rats. Moreover, a greater microglial density around A{beta} plaques and a less reactive phenotype was clearly observed at 11 in trained rats. These protective effects diminished by 19 months, coinciding with increased neuroinflammation and microglial dysfunction. At a molecular level, cognitive stimulation preserved PSD95 expression in male TgF344-AD and p-RPS6 in both sexes. ConclusionsPre-amyloid cognitive stimulation enhances synaptic plasticity, sustains brain network integrity, and modulates neuroinflammation, contributing to increased resilience against Alzheimers disease-related cognitive decline. In general, cognitive stimulation exerted a more protective effect in male TgF344-AD rats showing sex-dependent differences in pathology and cognitive reserve mechanisms. These findings highlight the importance of early cognitive engagement as a potential strategy to delay disease onset and underscore sex-specific differences in cognitive resilience mechanisms.

neuroscience↗

bioRxiv2024

Activation mapping in multi-center rat sensory-evoked functional MRI datasets using a unified pipeline.

Functional Magnetic Resonance Imaging (fMRI) in rodents is pivotal for understanding the mechanisms underlying Blood Oxygen Level-Dependent (BOLD) signals and phenotyping animal models of disorders, amongst other applications. Despite its growing use, comparing rodent fMRI results across different research sites remains challenging due to variations in experimental protocols. Here, we aggregated and analyzed 22 sensory-evoked rat fMRI datasets from 12 imaging centers, totaling scans from 220 rats, to assess the consistency of results across diverse protocols. We applied a standardized preprocessing pipeline and evaluated the impact of different hemodynamic response function models on group and individual level activity patterns. Our analysis revealed inter-dataset variability attributed to differences in experimental design, anesthesia protocols, and imaging parameters. We identified robust activation clusters in all (22/22) datasets. The comparison between stock human models implemented in software and rat-specific models showed significant variations in the resulting statistical maps. Our findings emphasize the necessity for standardized protocols and collaborative efforts to improve the reproducibility and reliability of rodent fMRI studies. We provide open access to all datasets and analysis code to foster transparency and further research in the field.

neuroscience↗

bioRxiv2019

Brain connectivity during Alzheimer’s disease progression and its cognitive impact in a transgenic rat model

The research of Alzheimers disease (AD) in their early stages and its progression till symptomatic onset is essential to understand the pathology and investigate new treatments. Animal models provide a helpful approach to this research, since they allow for controlled follow-up during the disease evolution. In this work, transgenic TgF344-AD rats were longitudinally evaluated starting at 6 months of age. Every 3 months, cognitive abilities were assessed by a memory-related task and magnetic resonance imaging (MRI) was acquired. Structural and functional brain networks were estimated and characterized by graph metrics to identify differences between the groups in connectivity, its evolution with age, and its influence on cognition. Structural networks of transgenic animals were altered since the earliest stage. Likewise, aging significantly affected network metrics in TgF344-AD, but not in the control group. In addition, while the structural brain network influenced cognitive outcome in transgenic animals, functional network impacted how control subjects performed. TgF344-AD brain network alterations were present from very early stages, difficult to identify in clinical research. Likewise, the characterization of aging in these animals, involving structural network reorganization and its effects on cognition, opens a window to evaluate new treatments for the disease. AUTHOR SUMMARYWe have applied magnetic resonance image based connectomics to characterize TgF344-AD rats, a transgenic model of Alzheimers disease (AD). This represents a highly translational approach, what is essential to investigate potential treatments. TgF344-AD animals were evaluated from early to advanced ages to describe alterations in brain connectivity and how brain networks are affected by age. Results showed that aging had a bigger impact in the structural connectivity of the TgF344-AD than in control animals, and that changes in the structural network, already observed at early ages, significantly influenced cognitive outcome of transgenic animals. Alterations in connectivity were similar to the described in AD human studies, and complement them providing insights into earlier stages and a plot of AD effects throughout the whole life span.

neuroscience↗