Biology subjects

Foddis, M.

Publications and source records attributed to Foddis, M..

5 recordsLinked to original sources

bioRxiv2025

Network Adaptability Governs Resilience and Susceptibility to Social Defeat

Stress resilience is defined as the ability to maintain mental health after adversity. In humans, resilience is marked by threat-safety discrimination and extinction of fear, whereas susceptibility involves fear generalization and extinction resistance. Using a translational mouse model of chronic social defeat stress combined with preregistered multimodal brain imaging, we investigated structural and network-level markers of resilience, susceptibility, and threat learning. Resilience was characterized by preserved dentate gyrus integrity, greater microstructural complexity in prefrontal regions, and signatures consistent with enhanced inhibitory gating within amygdalar circuits. Susceptibility, in contrast, involved reduced dentate gyrus complexity and diminished microstructural flexibility, with a weaker but parallel pattern in the basolateral amygdala. Impaired threat learning was linked to compromised CA1/CA2 integrity and reduced pons connectivity, highlighting hippocampal-brainstem interactions in memory consolidation. Overall, these findings show that resilience emerges from adaptive network reorganization, whereas susceptibility and impaired learning reflect distinct dysfunctions, underscoring individual coping differences even among genetically identical animals.

neuroscience↗

bioRxiv2025

Temporal dynamics of neuroplasticity and neurodegeneration in the central auditory system following noise-induced hearing loss: A multimodal imaging and histological study

Noise-induced hearing loss (NIHL) is a sensorineural disorder that triggers profound neuroplastic and neurodegenerative consequences in the central auditory nervous system (CNS). This study examined how neuronal density, axonal integrity and glutamatergic and GABAergic neurotransmission are affected after acute overstimulation in the central inferior colliculus (CIC) and the ventral medial geniculate body of the thalamus (MGV). To achieve this, a correlative multimodal approach combining audiometric, magnetic resonance imaging (MRI) and histological biomarkers was performed. Adult mice were noise-exposed to broadband white noise (5-20 kHz) for 3 hours at either high (115 dB SPL) or moderate (90 dB SPL) intensity, while unexposed mice were used as controls. Separate cohorts of mice were investigated 1-, 7-, 56- and 84-days post-exposure using in vivo magnetic resonance imaging (MRI) techniques: Voxel-based morphometry (VBM) of gray matter density (GMD), diffusion MRI (dMRI) of microstructure and connectivity, and single-voxel proton magnetic resonance spectroscopy (1H-MRS) for glutamate and GABA quantification. Frequency-specific auditory brainstem responses (ABR) were recorded at 4, 8, 16 and 32 kHz before and after exposure to examine hearing threshold (HT) shifts. Following imaging, brains were processed for fluorescence immunohistochemistry (FIHC) targeting Neuronal Nuclear Protein (NeuN), 4,6-diamidino-2-fenilindo (DAPI), Neurofilament (SMI312), vesicular GABA transporter (VGAT), and vesicular glutamate transporters 1 (VGLUT1) and 2 (VGLUT2). HTs were significantly elevated 7d, 56d and 84d after 115 dB noise exposure, suggesting a NIHL phenotype. Neurofilament density significantly increased in the CIC and MGV 1d after 115 dB noise exposure, and returned to baseline at later time points. dMRI transient microstructural alterations were observed 7d after 90 dB noise exposure. Glutamate and GABA decreases 84d after 90 dB exposure were also detected. Moreover, correlation analysis between audiometric, histological and MRI datasets revealed scarce relationships between the investigated parameters. These findings advance our understanding of the CNS adaptations of NIHL and emphasizes the need for more sensitive and integrative approaches to identify robust biomarkers of central auditory dysfunction.

neuroscience↗

bioRxiv2025

2-Deoxy-D-glucose chemical exchange-sensitive spin-lock MRI of cerebral glucose metabolism after stroke in the rat

Rapid breakdown of cerebral glucose metabolism is a hallmark in stroke pathology. Metabolic activity delineates the penumbra from the infarct core, representing tissue that is potentially salvageable by therapeutic interventions. Tools to image dynamics of glucose and its spatial distribution could provide biomarkers of disease severity and of the success of therapeutic interventions. Here, we developed a new protocol to measure glucose metabolism in a rat model of stroke using chemical exchange-sensitive spin-lock (CESL) MRI of the glucose analog 2-deoxy-D-glucose (2DG). We further implemented a protocol that combines 2DG-CESL-MRI with perfusion and diffusion MRI to relate this new signal to established definitions of hypoperfused tissue, cytotoxic edema and the penumbra. We found that 2DG-CESL-MRI provides a biomarker of disturbed glucose metabolism after stroke with high effect size. This is the first study to investigate CESL MRI of 2DG in the context of metabolism imaging in rodent stroke.

neuroscience↗

bioRxiv2024

Ide copy number variant does not influence lesion size and mortality in two C57BL/6J mouse models of cerebrovascular ischemia nor in human cerebrovascular disease. An exploratory study

Contrary to the common belief, the most commonly used laboratory mouse inbred strains are shaped by a distinctive genetic and phenotypic diversity. In the past 10 years next generation sequencing unveiled a wide spectrum of genetic variants in different mouse inbred strains and the meticulous observation of researchers pointed to a variegate intra-and inter-strain phenotypic diversity. Although a genotype-phenotype correlation has been described for some traits, the relationship between several endophenotypes and causative genetic variability remains still unknown. Recently, we characterized the brain collateral plasticity in two brain ischemia C57BL/6J mouse models (i.e bilateral common carotid artery stenosis [BCCAS] and 60-min transient unilateral middle cerebral artery occlusion [MCAO]) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) plasticity. Interestingly, a copy number variant (CNV) spanning Ide locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory. Given the critical role of Ide in vascular plasticity, Ide CNV was an excellent candidate to explain PcomA variability in C57BL/6J inbred mice. To investigate this hypothesis, we applied a combination of complementary techniques (i.e T2-weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) to characterize the collaterome in C57BL/6J BCCAS and MCAO mice and performed on these Taqman genotyping, exome sequencing, and RNA sequencing. We report an Ide CNV in a BCCAS mouse with 2 patent PcomAs. We then investigated the hypothesis that IDE gain and loss of function mutations may have influenced the vascular phenotype in a cohort of 438,250 cases and controls (UK Biobank) and 15,790 neurological patients (Genomics England), respectively. We identified four IDE CNVs resulting in a loss of function (LoF) in one patient with hereditary ataxia, a patient with hereditary congenital heart disease and two healthy individuals. In addition, we report four IDE LoF point mutations (p.Leu5X, p.Met394ValfsX29, p.Pro14SerfsX26, p.Leu889X) present in controls or inherited from healthy parents. Ide CNV and LoF variants do not crucially influence PcomA variability in C57BL/6J inbred mice and do not cause a vascular phenotype in humans.

genetics↗

bioRxiv2020

Vascular cognitive impairment in the mouse reshapes visual, spatial network functional connectivity.

Connectome analysis of neuroimaging data is a rapidly expanding field to identify disease specific biomarkers. Structural diffusion MRI connectivity has been useful in individuals with radiological features of small vessel disease, such as white matter hyperintensities. Global efficiency, a network metric calculated from the structural connectome, is an excellent predictor of cognitive decline. To dissect the biological underpinning of these changes, animal models are required. We tested whether the structural connectome is altered in a mouse model of vascular cognitive impairment. White matter damage was more pronounced by 6 compared to 3 months. Global efficiency remained intact, but the visual association cortex exhibited increased structural connectivity with other brain regions. Exploratory resting state functional MRI connectivity analysis revealed diminished default mode network activity in the model compared to shams. Further perturbations were observed in a primarily cortical hub and the retrosplenial and visual cortices, and the hippocampus were the most affected nodes. Behavioural deficits were observed in the cued water maze, supporting the suggestion that the visual and spatial memory networks are affected. We demonstrate specific circuitry is rendered vulnerable to vascular stress in the mouse, and the model will be useful to examine pathophysiological mechanisms of small vessel disease. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

neuroscience↗