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Boido, D.

Publications and source records attributed to Boido, D..

4 recordsLinked to original sources

Reduced tubulin polyglutamylation perturbs neuronal function and causes late-onset neurodegeneration

Microtubules are essential for neuronal functions and are involved in many neurodegenerative disorders. A posttranslational modification (PTM) of neuronal microtubules, polyglutamylation, was shown to control cargo transport, Tau protein binding to microtubules and to induce early-onset neurodegeneration when exceeding physiological levels. To determine the physiological importance of this PTM, we characterised mouse models with reduced polyglutamylation. We demonstrate that these mice develop late-onset atrophy of the olfactory bulb and frontal cortex, progressively reduced dendritic spine density, and deficits in olfaction, memory, and cognitive control. This indicates an important role of polyglutamylation in neuronal function. To test whether the observed defects are linked to neurodegeneration, we combined mice with reduced polyglutamylation with a transgenic model for tauopathy. Strikingly, reduced polyglutamylation accelerated the premature demise of mice transgenic for human Tau carrying the P301S mutation. Our work thus reveals key roles of microtubule polyglutamylation in neuronal function with implications for late-onset neurodegeneration linked to Tau pathology.

neuroscience↗

FAST BOLD FMRI REVEALS THE SPATIOTEMPORAL COMPLEXITY OF NEUROVASCULAR COUPLING ALTERATIONS IN CEREBRAL SMALL VESSEL DISEASE

Recent advances in neurophysiology highlighted the potential of high temporal resolution in Blood-Oxygen Level Dependent (BOLD) functional MRI (fMRI), although it is not yet standard practice. We demonstrated that fast BOLD fMRI can detect single-subject, single-stimulus visually evoked responses to brief stimuli at 3T. We used fast fMRI in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a genetic form of cerebral small vessel disease (cSVD). Using 2- and 10-second visual stimuli, we probed different neurovascular coupling regimes and showed that different regions of interest detect different facets of vascular dynamics. CADASIL patients showed significant changes in the amplitude and timing of the BOLD response, indicating early-age neurovascular impairment unrelated to anatomical lesions, and providing strong discriminative and generalization performance. These findings resolve prior inconsistencies in fMRI studies of CADASIL, supporting the use of fast fMRI to develop non-invasive biomarkers for cSVD and other neurodegenerative disorders.

neuroscience↗

A 3D-printed cradle for mouse preclinical MRI with an integrated water heating system

Functional Magnetic Resonance Imaging (fMRI) of small animals is mainly performed under sedation or anesthesia to avoid movement, which is detrimental to image quality. Heating systems to warm the animals usually rely on airflow or heating blankets or pads with circulating water to comply with MR compatibility requirements. However, these solutions are often suboptimal for small animals like mice scanned at ultra-high magnetic fields with long-bore MR scanners. We designed and built an MR cradle with an integrated water chamber, maximizing the contact surface with the mouses body. This large contact surface helps maintain body temperature without overheating the animal, thus reducing the risk of burns and hyperthermia. Our cradle keeps the mouses body temperature stable within the physiological range during an MRI session and fits the bore of a Bruker 17.2T scanner. We share the 3D drawings and all the information needed to replicate the cradle. Our design can be adapted to work on preclinical scanners with similar bore sizes and customized to add stimulation devices.

neuroscience↗

Iliski, a software for robust calculation of transfer functions

1.Understanding the relationships between biological events is paramount to unravel pathophysiological mechanisms. These relationships can be modeled with Transfer Functions (TFs), with no need of a priori hypotheses as to the shape of the transfer function. Here we present Iliski, a software dedicated to TFs computation between two signals. It includes different pre-treatment routines and TF computation processes: deconvolution, deterministic and non-deterministic optimization algorithms that are adapted to disparate datasets. We apply Iliski to data on neurovascular coupling, an ensemble of biological events that link neuronal activity to local changes of blood flow, highlighting the software benefits and caveats in the computation and evaluation of TFs. We also propose a workflow that will help users to choose the best computation according to the dataset. Iliski is available under the open-source license CC BY 4.0 on GitLab (https://gitlab.com/AliK_A/iliski) and can be used on the most common operating systems, either within the MATLAB environment, or as a standalone application.

bioinformatics↗