Biology subjects

Ciobanu, L.

Publications and source records attributed to Ciobanu, L..

9 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

An Ultra-High-Resolution 17.2 T MRI Atlas (HypoAtlas) and Multimodal Pipeline to Study the Mouse Hypothalamus: Sexual Dimorphism and Lateralization Insights

Structural and functional insights into the mouse hypothalamus are hampered by its small size and deep location. Here, we leverage ultra-high-field magnetic resonance imaging (UHF-MRI) at 17.2 Tesla to achieve unprecedented spatial resolution in structural, functional and neurochemical imaging of the mouse hypothalamus, including sexual dimorphism in certain nuclei. High-resolution ex vivo anatomical MRI enabled precise hypothalamic parcellation, improving on existing atlases and revealing nuclei previously unresolved by MRI. Diffusion MRI and tractography mapped intra- and extra-hypothalamic pathways, facilitating circuit-level exploration without a priori assumptions. Resting-state fMRI combined with independent component analysis identified novel hypothalamic networks, demonstrating the enhanced capacity of UHF MRI to detect deep-brain activity. {superscript 1}H-magnetic resonance spectroscopy quantified neurochemical profiles, revealing sexually dimorphic heterogeneity within the hypothalamus. Our comprehensive multimodal approach uncovers sex differences in hypothalamic anatomy, microstructure, and neurochemistry, emphasizing the importance of sex as a biological variable. This integrated pipeline offers a valuable resource for dissecting hypothalamic circuits and functions, advancing our understanding of neuroendocrine regulation, behavior, and disease mechanisms, with direct translational relevance.

neuroscience↗

bioRxiv2025

Problem-solving without a cortex: inferior lobe drives goal-directed object manipulation in cichlid fish

Goal-directed object manipulation and problem-solving, which are necessary to evolve tool use behaviors, have long been linked to the expansion of the telencephalon in mammals and birds. Here, we show that goal-directed object manipulation in cichlid fish is driven by a non-telencephalic brain structure, the inferior lobe. Using manganese-enhanced MRI (MEMRI) on an ultra-high field 17.2 Tesla MRI system, we show that the inferior lobe is activated during a puzzle-box opening task. Furthermore, magnetic resonance (MR)-guided High Intensity Focused Ultrasound (HIFU) lesions profoundly impair fine motor coordination during this task without affecting general locomotion or motivation. These results reveal that cortex-like cognitive functions can arise from non-telencephalic brain structures in teleosts. With no homolog in tetrapods, the inferior lobe is a critical hub for flexible behavior in teleost fish. Our findings highlight the existence of alternative neural architectures for the emergence of complex cognition.

neuroscience↗

bioRxiv2025

Functional Brain Imaging and Targeted Lesion Studies Using Manganese-Enhanced MRI and Focused Ultrasound in Non-Conventional ModelSpecies

Linking behavior to its neuroanatomical basis in non-conventional model species remains a significant challenge due to the scarcity of imaging and molecular tools. Commonly used approaches such as electrophysiological recordings rely on precise stereotaxic atlases or species-specific antibodies, while optogenetics requires transgenic lines which are largely unavailable beyond classical model organisms (e.g., mice, rats, zebrafish). Moreover, surgical lesion studies, a staple for verifying brain structure and behavior relationships, are logistically complex in species lacking atlases or living in aquatic environments. Here, we present a protocol integrating Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) and MR-guided High-Intensity Focused Ultrasound (HIFU) to overcome these limitations, which we demonstrate in the convict cichlid (Amatitlania nigrofasciata), a teleost fish lacking conventional neuroscience tools. MEMRI enables non-invasive, sub-millimeter resolution mapping of brain activity during behavior, and HIFU facilitates precise, surgery-free lesioning of targeted regions, adaptable to species without stereotaxic atlases. This combined approach offers a versatile, broadly applicable framework for linking brain structure and behavior in non-model organisms, advancing evolutionary and comparative neuroscience.

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↗

bioRxiv2020

Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins

The critical role of blood lipids in a broad range of health and disease states is well recognised, while an understanding of the complex genetic regulation of lipid homeostasis is emerging. Traditional blood lipids (LDL-C, HDL-C and triglycerides) are known to be substantially regulated by genetic variation. Less well explored is the interplay of genetics and environment within the broader blood lipidome. Here we use the twin model to examine heritability of the plasma lipidome among healthy older aged twins and explore gene expression and epigenetic (DNA methylation) associations of these lipids. Heritability of 209 plasma lipids quantified by liquid chromatography coupled mass spectrometry (LC-MS) was assessed in 75 monozygotic and 55 dizygotic twin pairs enrolled in the Older Australian Twins Study (OATS), aged 69-93 years. Only 27/209 lipids (13.3%) were significantly heritable under the classical ACE twin model (h2 = 0.28-0.59). Ceramides (Cer) and triglycerides (TG) were most heritable, while sphingomyelins (SM) and most phospholipids, especially lysophospholipids, were not significantly heritable. Lipid levels correlated with 3731 transcripts. Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, which were not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for a proportion of variability in some non-heritable lipids, especially lysophosphatidylcholine (LPC). We found a complex interplay of genetic and environmental influences on the ageing plasma lipidome, with most of the variation controlled by unique environmental influences.

genetics↗

bioRxiv2020

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.

The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its dysfunction might lead to several brain pathologies, including the Alzheimers disease. A key component of the GS and brain tissue water circulation is the astrocyte which is regulated by acquaporin4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo and non-invasively.

neuroscience↗

bioRxiv2020

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and Diffusion fMRI responses in rat visual cortex

The contribution of astrocytes to the BOLD fMRI and DfMRI responses in visual cortex of mice following visual stimulation were investigated an aquaporin 4 (AQP4) channel blocker, TGN-020, acting as an astrocyte function perturbator. Under TGN-020 injection the amplitude of the BOLD fMRI response became significantly higher. In contrast no significant changes in the DfMRI responses and the electrophysiological responses were observed. Those results further confirm the implications of astrocytes in the neurovascular coupling mechanism underlying BOLD fMRI, while DfMRI relies on other, not astrocyte-mediated mechanisms.

neuroscience↗

bioRxiv2018

BIN1 genetic risk factor for Alzheimer is sufficient to induce early structural tract alterations in entorhinal cortex-dentate gyrus pathway and related hippocampal multi-scale impairments

Genetic factors are known to contribute to Late Onset Alzheimers disease (LOAD) but their contribution to pathophysiology, specially to prodomic phases accessible to therapeutic approaches are far to be understood. To translate genetic risk of Alzheimers disease (AD) into mechanistic insight, we generated transgenic mouse lines that express a [~]195 kbp human BAC that includes only BIN1, a gene associated to LOAD. This model gives a modest BIN1 overexpression, dependent of the number of BAC copies. At 6 months of age, we detected impaired entorhinal cortex (EC)-hippocampal pathways with specific impairments in EC-dentate gyrus synaptic long-term potentiation, dendritic spines of granular cells and recognition episodic memory. Structural changes were quantified using MRI. Their whole-brain functional impact were analyzed using resting state fMRI with a hypoconnectivity centered on entorhinal cortex. These early phenotype defects independent of any changes in A-beta can be instrumental in the search for new AD drug targets.

neuroscience↗