Biology subjects

Tachrount, M.

Publications and source records attributed to Tachrount, M..

8 recordsLinked to original sources

bioRxiv2026

High-throughput light-sheet 3D microscopy of whole rodent brain microstructure for integration with MRI

Whole-brain cellular mapping is essential for understanding how differences in cellular architecture shape brain organisation and function. Magnetic Resonance Imaging (MRI) provides whole-brain coverage in humans and animal models but is only indirectly sensitive to cellular features. Integrating MRI with whole-brain microscopy is therefore critical for interpreting existing microstructural MRI metrics and developing new, more specific ones. Here, we present a scalable cross-resolution framework that integrates 3D light-sheet microscopy (LSM) of intact rodent brains with diffusion MRI (dMRI) to bridge cellular and macroscopic brain imaging. By combining active electrotransport-based tissue clearing and immunolabelling with accelerated LSM acquisitions, we achieve whole-brain multiplexed mapping of neuronal and glial populations in intact rodent brains on timescales comparable to conventional histology and 2D microscopy. This throughput enables LSM and MRI integration at scale, linking macroscopic MRI contrasts to microscopic cellular features within the same tissue. We apply this framework across eight genetically diverse mouse strains to develop predictive models of 3D microscopy-derived cellular features from multi-shell dMRI-derived contrasts. We demonstrate that data-driven combinations of state-of-the-art dMRI contrasts predict neuronal and astrocytic features better than individual contrasts, across all animals. Our novel approach enables 3D microscopy to guide the development and interpretation of microstructural MRI measures that are ultimately translatable to the living human brain.

neuroscience↗

bioRxiv2026

Longitudinal neurochemical profiling after experimental stroke using edited MR spectroscopy

Background: Alterations in excitatory and inhibitory neurotransmission contribute to stroke pathology and recovery, yet longitudinal assessment of these changes in vivo remains limited. We investigated the feasibility of longitudinal edited proton magnetic resonance spectroscopy (1H-MRS) to quantify {gamma}-aminobutyric acid (GABA) and glutamate following experimental focal cerebral ischaemia. Methods: Male rats underwent endothelin-1-induced striatal ischaemia or sham surgery. Longitudinal edited 1H-MRS was performed at baseline and 2-, 7- and 30-days post-stroke at 7-tesla with a MEGA-sLASER sequence. A voxel was positioned within the ipsilesional motor cortex adjacent to the lesion. Behavioural outcomes (grip strength, adhesive removal and CatWalk gait analysis) were assessed alongside spectroscopy, and immunohistochemistry for Iba1, GFAP and ICAM-1 was performed at 30 days. Results: Stroke induced a transient reduction in GABA+/tCr within the ipsilesional motor cortex, with significantly lower concentrations than sham animals at 7 days (p<0.05), returning to baseline by 30 days. Glutamate/tCr and GABA/glutamate ratio were unchanged throughout the study. Behavioural deficits were mild, with significant effects on motor outcomes such as grip strength, gait swing speed and paw placement, while sensory areas of the brain seemed largely unaffected. Histological analysis revealed no persistent differences in cortical Iba1, GFAP or ICAM-1 immunoreactivity at 30 days. Conclusions: Longitudinal 1H-MRS is a feasible approach for monitoring dynamic changes in inhibitory neurochemistry following experimental stroke. The transient reduction in peri-lesional GABA, despite minimal behavioural impairment and an absence of persistent cortical inflammation, supports the use of edited spectroscopy as a translational tool to investigate neurochemical mechanisms underlying network dynamics in post-stroke recovery.

neuroscience↗

bioRxiv2026

A hippocampal neuroimaging signature of neurovascular insulin signalling links metabolism to mood

Depression is a leading cause of global disability and is increasingly linked to systemic metabolic dysfunctions, including insulin resistance. However, the biological pathways connecting metabolic state to affective symptoms are unresolved. A growing body of evidence indicates that insulin, beyond its role in systemic glucose homeostasis, supports brain metabolism, synaptic function and cognition, yet its contribution to mood regulation remains unclear. Here, we identify a human hippocampal metabolic signature associated with glycaemic variation in individuals with depression. Using multimodal neuroimaging, we show that hippocampal concentrations of GABA and lactate correlate with HbA1c and with mood severity, while functional connectivity between the hippocampus and the default mode network tracks affective symptoms independently of adiposity. To causally probe these relationships, we generated a mouse model of hippocampus-specific insulin receptor depletion. Unexpectedly, reducing insulin signalling at the blood brain barrier enhanced neuronal metabolism and attenuated anxiety-like behaviour. Notably, hippocampal lactate and GABA levels similarly tracked anxiety-related behaviour in mice, mirroring their association with symptom severity in humans. Together, these findings identify a conserved neurometabolic signature linking hippocampal insulin signalling to affective state, and reveal that brain insulin resistance exerts context- and cell-type-specific effects on behaviour. This work establishes a mechanistic basis for brain insulin resistance in depression and highlights the hippocampus as a critical hub for metabolic modulation of mood.

neuroscience↗

bioRxiv2026

Ultrasound-mediated focal serotonin delivery causally modulates motivation in primates

Causal manipulation of neuromodulatory systems has been constrained by a trade-off between spatial precision and translational relevance: circuit-specific techniques are invasive, whereas systemic pharmacology lacks anatomical specificity. Here, we establish ultrasound-mediated neuromodulator delivery as a non-invasive, spatially precise approach for causal neuropharmacology in awake, behaving primates. By transiently opening the blood-brain barrier, we delivered systemically administered serotonin to the perigenual anterior cingulate cortex (pgACC) during a decision-making task. Combining computational modelling with multimodal imaging, pupillometry and histology, we show that elevating pgACC serotonin altered local neural activity and weakened the influence of reward environment on motivational state while leaving sensitivity to immediate reward opportunities intact. This was accompanied by reduced functional coupling, decreased local glutamatergic metabolite signal and increased serotonergic signal at the target, with repeated delivery well tolerated. Together, these findings establish a translatable platform for focal neuropharmacology and identify pgACC serotonin as a regulator of context-dependent motivation.

neuroscience↗

bioRxiv2026

Non-invasive measurement of neurotransmitter-specific glucose metabolism in the human brain using proton-observed proton-edited 13C-MRS (POPE13C-MRS)

Non-invasive measurement of neurotransmitter-specific glucose metabolism in the human brain remains a major challenge, limiting mechanistic insight into excitatory-inhibitory imbalance across neurological and psychiatric disorders. Existing approaches either lack neurotransmitter specificity or require specialised hardware that constrains clinical applicability. Here, we introduce proton-observed proton-edited 13C magnetic resonance spectroscopy (POPE13C-MRS), an approach that enables non-invasive detection of glutamate, GABA, and lactate metabolism using standard proton MRI hardware. The method combines administration of 13C-labelled glucose with targeted proton editing to detect 1H-13C satellite resonances. Using a cross-species proof-of-concept approach, we demonstrate consistent detection of neurotransmitter-specific 13C labelling in mice and feasibility in the human brain at ultra-high field. POPE13C-MRS provides a readout of glutamatergic and GABAergic metabolism, enabling in vivo assessment of excitatory-inhibitory metabolic balance. This establishes a means for probing neurometabolic coupling with potential applications in translational and clinical neuroscience.

neuroscience↗

bioRxiv2024

In vivo quantification of creatine kinase kinetics in mouse brain using 31P-MRS at 7 Tesla

31P-MRS is a method of choice for studying neuroenergetics in vivo, but its application in the mouse brain have been limited, often restricted to ultra-high field (>7 Tesla) MRI scanners. Establishing its feasibility on more readily available preclinical 7 Tesla (T) scanners would create new opportunities to study metabolism and physiology in murine models of brain disorders. Here, we demonstrate that the apparent forward rate constant (kf) of creatine kinase (CK) can be accurately quantified using a progressive saturation-transfer approach in the mouse brain at 7T. We also find that a reduction of approximately 20% in the breathing rate of anesthetized mice can lead to a 36% increase in kf attributable to a drop in intracellular pH and mitochondrial ATP production. To achieve this, we used a test-retest analysis to assess the reliability and repeatability of 31P-MRS acquisition, analysis and experimental design protocols. We report that most 31P-containing metabolites can be reliably measured using a localized 3D-ISIS sequence, which showed highest SNR amplitude, SNR consistency and minimal T2 relaxation signal loss. Using this protocol, our study identifies, for the first time, key physiological factors influencing mouse brain energy homeostasis in vivo and provides a methodological basis that will guide future studies interested in implementing 31P-MRS on preclinical 7T scanners.

neuroscience↗

bioRxiv2021

Mapping prion pathology in mice using quantitative imaging: an MRI study

Human prion diseases are fatal neurodegenerative disorders which cause cognitive impairment and neurological deficits. Additional measures of tissue status are necessary for improving the sensitivity and specificity of clinical diagnosis as in many cases clinical forms of prion disease are commonly mistaken for other forms of dementia. To that effect, we developed a set of quantitative magnetic resonance-based tools, including magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and quantitative T1 and T2 imaging to study the course of the disease in an animal model of prion disease. Using in vivo MTR, significant changes were detected in the cortex and thalamus of late-stage prion -infected mice as compared to littermates. In addition, we found a significant increase of MTR in thalamus and cortex of 80 dpi healthy mice when compared with 160 dpi healthy mice suggestive of changes occurring during the development of the brain. Using quantitative T2 mapping, significantly higher values were measured in thalamus of prion mice at all stages of the disease (T2=40ms) while T1 was found to be significantly higher in cortex (T1=1.89s) and hippocampus, albeit only in late-stage prion mice as compared to aged-matched controls (T1=1.67s). Using quantitative MRS significant changes were detected in glutamate (Glu) and myo-inositol (Ins) at all stages of prion disease when compared with the control group. NAA, Cr, Lactate and Lipids were only found to be significantly different at early and late stages of the disease while Taurine (Tau) was only significantly increased in the asymptomatic stage without any significant change at early and late stages of the disease. These changes in MRI and MRS signals, which precede clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.

biophysics↗

bioRxiv2021

Can Chemical Exchange Saturation Transfer (CEST MRI) be used as biomarker of disease progression in Prion Disease?

Human prion diseases are fatal neurodegenerative disorders that may have prolonged asymptomatic incubation periods. However, the underlying mechanism by which prions cause brain damage remains unclear. In turn, characterization of early pathological aspects would be of benefit for the diagnosis and potential treatment of these progressive neurodegenerative disorders. We investigated chemical exchange saturation transfer (CEST) MRI based on its exquisite sensitivity to cytosol protein content as a surrogate for prion disease pathology. Three groups of prion-infected mice at different stages of the disease underwent conventional magnetic resonance imaging and CEST MRI at 9.4T. For each mouse, chemical exchange contrasts were measured by applying five RF powers at various frequency offsets using magnetization transfer asymmetries. Relayed Nuclear Overhauser effects (NOE*) and amide proton transfer (APT*) were also assessed. For comparison, CEST MRI measurements were also made in healthy control mice brains. Here we show that alterations in CEST signal were detected before structural modifications or any clinical signs of prion disease. The detected CEST signal displayed different patterns at different stages of the disease indicating its potential for use as a longitudinal marker of disease progression. Highly significant correlations were found between CEST metrics and histopathological findings. A decline in NOE signal was positively correlated with abnormal prion protein deposition (R2 = 0.91) in the thalami of prion infected mice. Moreover, the NOE signal was negatively correlated with astrogliosis (R2 = 0.71) in the thalamus. No significant correlations were detected between NOE signals and spongiosis. MTR asymmetry at 3.5 ppm was also correlated with astrogliosis (R2 = 0.59), and prion protein deposition (R2 = 0.63) in thalamus. No significant changes were detected in APT* between prion-infected and control mice at all stages of the disease. Finally, MTR asymmetry between 2.8 and 3.2 ppm was correlated with prion protein deposition (R2 = 0.47) in the thalamus of prion -infected mice. To conclude, CEST MRI has potential utility as a biomarker of neurodegenerative processes in prion disease.

biophysics↗