@article{pmid41318997,

title = {The impact of tau deletion on Huntington's disease: An in vivo perspective},

author = {Eva Lepinay and Martine Saint-Pierre and Maxime Teixeira and Marta Snapyan and Abid Oueslati and Martin Parent and Melanie Alpaugh and Francesca Cicchetti},

doi = {10.1016/j.ymthe.2025.11.033},

issn = {1525-0024},

year  = {2025},

date = {2025-11-01},

journal = {Mol Ther},

abstract = {Although an emerging body of evidence suggests that abnormal forms of tau are present and contribute to Huntington's disease (HD)-a genetic neurodegenerative disorder primarily characterized by the aggregation of the mutant huntingtin (mHtt) protein affecting cognitive, motor, and psychiatric function-it is not clear to what extent this is relevant to the disease phenotype, and hence future treatments. We therefore generated a novel murine model by crossing heterozygous zQ175 knockin HD mice with homozygous tau knockout mice (mTKO). Tau deletion exacerbated both motor and cognitive deficits in zQ175/mTKO mice, which was accompanied by increased mHtt aggregation and alterations in microtubule dynamics, including dysregulated expression of microtubule-associated proteins, aberrant perinuclear β-tubulin accumulation, and microtubule destabilization. Combined, our findings unveil a previously unrecognized protective role of non-hyperphosphorylated tau in maintaining cytoskeletal homeostasis in HD and highlight a functional overlap between tau and huntingtin in regulating aggregate dynamics and cytoskeletal integrity. Our findings complement previous reports suggesting that reducing tau levels could mitigate disease pathology in HD mouse models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41043993,

title = {Distinct ultrastructural properties and plasticity of synapses formed by adult-born and early-born interneurons in the mouse olfactory bulb},

author = {Marta Snapyan and Vlad-Stefan Constantinescu and Armen Saghatelyan and Martin Parent},

doi = {10.1523/JNEUROSCI.1358-24.2025},

issn = {1529-2401},

year  = {2025},

date = {2025-10-01},

journal = {J Neurosci},

abstract = {The olfactory bulb (OB) is one of the few regions in the adult brain that receives newly generated neuronal precursors throughout the lifespan of animals. These neuronal precursors differentiate into OB interneurons, mostly granule cells (GCs), and integrate into the bulbar network by forming dendro-dendritic reciprocal synapses with OB principal neurons. The ultrastructural properties and plasticity of these synapses and whether they are distinct from those formed by early-born, resident GCs remain unknown. In the present study, we assessed the ultrastructural properties of dendro-dendritic reciprocal synapses formed by either adult-born or resident, early-born GCs with principal neurons in mice of both sexes and studied their plasticity following sensory deprivation and odor learning. The synapses formed by either adult-born or resident, early-born GCs with principal bulbar neurons were undistinguishable in terms of area, diameter, and aspect ratio. In contrast, the synapses formed by adult-born GCs were characterized by a smaller synaptic cleft and a larger density of total and docked synaptic vesicles than synapses formed by resident GCs. Sensory deprivation and odor learning decreased and increased, respectively, the overall density and the number of docked synaptic vesicles in adult-born and resident GCs forming synapses with principal neurons. Our results revealed important differences in the ultrastructural properties of synapses formed by interneurons born at distinct developmental stages and revealed their plasticity in response to sensory deprivation and odor learning. The adult-born neurons in the olfactory bulb play an important role in the bulbar network functioning and odor behavior. In this work, we characterized the ultrastructural properties of synapses formed by adult-born and resident or early-born interneurons with bulbar principal cells and assessed their plasticity following sensory deprivation and odor learning. We revealed marked differences in synapses formed by adult-born interneurons that are characterized by increased density of synaptic vesicles and higher number of docked vesicles as compared to synapses formed by resident, early-born interneurons. We also showed their plasticity following sensory deprivation and odor learning. Our data provide insights for exquisite implication of adult-born interneurons in the odor information processing and odor behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41256884,

title = {Millennium Pathways for Tractography: 40 grand challenges to shape the future of tractography},

author = {Maxime Descoteaux and Kurt G Schilling and Dogu Baran Aydogan and Christian Beaulieu and Elena Borra and Maxime Chamberland and Alessandro Daducci and Alberto De Luca and Flavio Dell'Acqua and Jessica Dubois and Tim B Dyrby and Shawna Farquharson and Stephanie Forkel and Martijn Froeling and Alessandra Griffa and Mareike Grotheer and Pamela Guevara and Suzanne N Haber and Vinod Kumar Jangir and Alexander Leemans and Joël Lefebvre and Ching-Po Lin and Graham Little and Chun-Yi Zac Lo and Chiara Maffei and Helen S Mayberg and Jennifer A McNab and Pratik Mukherjee and Lauren J O'Donnell and Martin Parent and Carlo Pierpaoli and Francois Rheault and Kathleen S Rockland and Alard Roebroeck and Ariel Rokem and R Jarrett Rushmore and Silvio Sarubbo and Simona Schiavi and Stamatios N Sotiropoulos and Diego Szczupak and Michel Thiebaut de Schotten and J-Donald Tournier and Francesco Vergani and Joseph Yuan-Mou Yang and Fan Zhang and Derek Jones and Laurent Petit},

issn = {2331-8422},

year  = {2025},

date = {2025-09-01},

journal = {ArXiv},

abstract = {In the spirit of the historic  that heralded a new era for mathematics, the newly formed International Society for Tractography (IST) has launched the , a community-driven roadmap designed to shape the future of the field. Conceived during the inaugural , this initiative reflects a collective vision for advancing tractography over the coming decade and beyond. The roadmap consists of 40 grand challenges, developed by international experts and organized into seven categories spanning three overarching themes: neuroanatomy, tractography methods, and clinical applications. By defining shared short-, medium-, and long-term goals, these pathways provide a structured framework to confront fundamental limitations, promote rigorous validation, and accelerate the translation of tractography into a robust tool for neuroscience and medicine. Ultimately, the  aim to guide and inspire future research and collaboration, ensuring the continued scientific and clinical relevance of tractography well into the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40735541,

title = {Catheter-based polarimetric imaging to complement MRI for deep brain stimulation neurosurgery},

author = {Shadi Masoumi and Maxina Sheft and Mireille Quémener and Alexandre Bédard and Valérie Pineau Noël and Martin Parent and Martin Villiger and Daniel C Côté},

doi = {10.1117/1.NPh.12.3.035001},

issn = {2329-423X},

year  = {2025},

date = {2025-07-01},

journal = {Neurophotonics},

volume = {12},

number = {3},

pages = {035001},

abstract = {SIGNIFICANCE: Deep brain stimulation (DBS) is an established treatment for movement disorders and other neurological conditions. Accurate localization of small deep brain nuclei, such as the subthalamic nucleus (STN) and internal pallidum (GPi), is crucial for successful DBS outcomes. However, magnetic resonance imaging (MRI), commonly used for DBS planning, lacks the resolution and contrast needed to directly delineate these target structures.nnAIM: We aim to explore the potential of catheter-based polarization-sensitive optical coherence tomography (PS-OCT) as a complementary imaging tool for high-resolution visualization of tissue surrounding the DBS insertion trajectory.nnAPPROACH: We simulated DBS implantation surgery at three targets in a post-mortem nonhuman primate head. PS-OCT, using advanced reconstruction algorithms for absolute depth-resolved birefringence, was compared with MRI for its ability to visualize and differentiate structural details.nnRESULTS: PS-OCT provided more detailed and accurate structural information than MRI while maintaining consistency with MRI results. Its compact form factor and imaging paradigm integrate seamlessly into the surgical workflow, offering new insights for intraoperative decision-making.nnCONCLUSIONS: PS-OCT functions as an intraoperative imaging tool, offering valuable guidance during the procedure. These findings establish PS-OCT as a promising complementary tool for DBS, with potential for further clinical validation and  studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40459517,

title = {Mapping Caudolenticular Gray Matter Bridges in the Human Brain Striatum Through Diffusion Magnetic Resonance Imaging and Tractography},

author = {Graham Little and Charles Poirier and Arnaud Bore and Martin Parent and Laurent Petit and Maxime Descoteaux},

doi = {10.1002/hbm.70245},

issn = {1097-0193},

year  = {2025},

date = {2025-06-01},

journal = {Hum Brain Mapp},

volume = {46},

number = {8},

pages = {e70245},

abstract = {In primates, the putamen and the caudate nucleus are connected by ~1 mm-thick caudolenticular gray matter bridges (CLGBs) interspersed between the white matter bundles of the internal capsule. Little is understood about the functional or microstructural properties of the CLGBs. In studies proposing high resolution diffusion magnetic resonance imaging (dMRI) techniques, CLGBs have been qualitatively identified as an example of superior imaging quality; however, the microstructural properties of these structures have yet to be examined. In this study, it is demonstrated for the first time that dMRI is sensitive to an organized anisotropic signal oriented in the direction parallel to the CLGBs, suggesting that dMRI could be a useful imaging method for probing the microstructure of the CLGBs. To demonstrate the anisotropic diffusion signal is coherently organized along the extent of the CLGBs and to enable a subsequent CLGB microstructural measurement, a customized tractography seeding and filtering method is proposed that utilizes the shape of the human striatum (putamen + caudate nucleus) to reconstruct the CLGBs in 3D. The proposed seeding strategy seeds tractography streamlines outward and normal to the surface of a 3D model of the striatum such that reconstructed streamlines are more likely to follow the diffusion signal peaks aligned parallel to the CLGBs. The method is applied to three different diffusion datasets, namely a high resolution 760 μm isotropic diffusion dataset acquired on a single subject, the test-retest cohort included as part of the human connectome project (N = 44) with diffusion data acquired at 1.25 mm isotropic, and a locally acquired "clinical" test-retest dataset acquired at 2.0 mm isotropic (N = 24). Reconstructed CLGBs directly overlap expected gray matter regions in the human brain for all three datasets. In addition, the method is shown to accurately reconstruct CLGBs repeatedly across multiple test-retest cohorts. The tractography CLGB reconstructions are then used to extract a quantitative measurement of microstructure from a local model of the diffusion signal along the CLGBs themselves. This is the first work to comprehensively study the CLGBs in vivo using dMRI and presents techniques suitable for future human neuroscience studies targeting these structures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40445394,

title = {Brain connectivity: complex, not chaotic},

author = {Elena Borra and Derek K Jones and Martin Parent and Laurent Petit and Kathleen S Rockland and R Jarrett Rushmore and Diego Szczupak},

doi = {10.1007/s00429-025-02943-3},

issn = {1863-2661},

year  = {2025},

date = {2025-05-01},

journal = {Brain Struct Funct},

volume = {230},

number = {5},

pages = {77},

abstract = {The term "connections" is a commonly used and convenient shorthand for describing the complex organization of the brain, but it can easily lead to an overemphasis on pairwise or point-to-point, source-target network connectivity. Anatomical studies make clear that there are other important features to consider such as divergence and collateralization (axons or bundles branching to multiple targets), convergence (multiple bundles from different sources converging on the same target), and scrambled topography along a trajectory. This short "Did You Know" communication elaborates on several of these features from the anatomical perspective, while inviting continued dialogue with the tractography community in addressing the shared goals of better understanding brain organization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39829080,

title = {Adult Neurogenesis in the Subventricular Zone of Patients with Huntington's and Parkinson's Diseases and following Long-Term Treatment with Deep Brain Stimulation},

author = {Marta Snapyan and Francis Desmeules and Jonathan Munro and Morgan Bérard and Stephan Saikali and Peter V Gould and Maxime Richer and Emmanuelle Pourcher and Mélanie Langlois and Anne-Marie Dufresne and Michel Prud'homme and Léo Cantin and André Parent and Armen Saghatelyan and Martin Parent},

doi = {10.1002/ana.27181},

issn = {1531-8249},

year  = {2025},

date = {2025-05-01},

journal = {Ann Neurol},

volume = {97},

number = {5},

pages = {894--906},

abstract = {OBJECTIVE: Parkinson's and Huntington's diseases are characterized by progressive neuronal loss. Previous studies using human postmortem tissues have shown the impact of neurodegenerative disorders on adult neurogenesis. The extent to which adult neural stem cells are activated in the subventricular zone and whether therapeutic treatments such as deep brain stimulation promote adult neurogenesis remains unclear. The goal of the present study is to assess adult neural stem cells activation and neurogenesis in the subventricular zone of patients with Huntington's and Parkinson's diseases who were treated or not by deep brain stimulation.nnMETHODS: Postmortem brain samples from Huntington's and Parkinson's disease patients who had received or not long-term deep brain stimulation of the subthalamic nucleus were used.nnRESULTS: Our results indicate a significant increase in the thickness of the subventricular zone and in the density of proliferating cells and activated stem cells in the brain of Huntington's disease subjects and Parkinson's disease patients treated with deep brain stimulation. We also observed an increase in the density of immature neurons in the brain of these patients.nnINTERPRETATION: Overall, our data indicate that long-term deep brain stimulation of the subthalamic nucleus promotes cell proliferation and neurogenesis in the subventricular zone that are reduced in Parkinson's disease. Taken together, our results also provide a detailed characterization of the cellular composition of the adult human subventricular zone and caudate nucleus in normal condition and in Parkinson's and Huntington's diseases and demonstrate the plasticity of these regions in response to neurodegeneration. ANN NEUROL 2025;97:894-906.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40331237,

title = {Retinal changes detected by diffuse reflectance spectroscopy in parkinsonian monkeys},

author = {Jonathan Munro and Elahe Parham and Damon DePaoli and Nicolas Lapointe and Cleophace Akitegetse and Shirley Fecteau and Dominic Sauvageau and Thérèse Di Paolo and Daniel C Côté and Martin Parent},

doi = {10.1117/1.NPh.12.2.025008},

issn = {2329-423X},

year  = {2025},

date = {2025-04-01},

journal = {Neurophotonics},

volume = {12},

number = {2},

pages = {025008},

abstract = {SIGNIFICANCE: Parkinson's disease (PD) is diagnosed when 50% neurodegeneration has occurred. The retina could provide biomarkers that would allow for earlier diagnosis. Retinal spectroscopy is a technique that could be used to find such biomarkers.nnAIM: We aimed to find new diagnostic biomarkers for PD following detailed spectral examinations of the retina.nnAPPROACH: The newly developed Zilia Ocular device was used to perform spectrometric scans of the optic nerve head (ONH) and the retina of four cynomolgus monkeys () before and after the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin used to produce the gold-standard animal model of PD. From the spectrometric data, the blood oximetry was calculated, and the diffuse reflectance spectra (DRS) were analyzed to find variations between the two experimental conditions. Post-mortem analyses were also performed on the retina of the four parkinsonian monkeys and four additional control animals.nnRESULTS: The analysis of the DRS indicated a lower slope between the 480- and 525-nm wavelengths in both the ONH and the retina. Post-mortem measurements of the retinal layer thicknesses showed that the outer nuclear layer was significantly thinner in MPTP-intoxicated monkeys, compared with controls. Altogether, these results indicate that MPTP altered the optical properties of the ONH and the retina and show that these variations might be explained by MPTP-induced structural changes in the eye fundus, as observed post-mortem.nnCONCLUSIONS: Overall, our results indicate that spectroscopy could be used as a noninvasive method to detect changes in the retina that occur in PD and that such changes could represent retinal biomarkers for improved diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39719704,

title = {A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion},

author = {Anna Flury and Leen Aljayousi and Hye-Jin Park and Mohammadparsa Khakpour and Jack Mechler and Siaresh Aziz and Jackson D McGrath and Pragney Deme and Colby Sandberg and Fernando González Ibáñez and Olivia Braniff and Thi Ngo and Simira Smith and Matthew Velez and Denice Moran Ramirez and Dvir Avnon-Klein and John W Murray and Jia Liu and Martin Parent and Susana Mingote and Norman J Haughey and Sebastian Werneburg and Marie-Ève Tremblay and Pinar Ayata},

doi = {10.1016/j.neuron.2024.11.018},

issn = {1097-4199},

year  = {2025},

date = {2025-02-01},

journal = {Neuron},

volume = {113},

number = {4},

pages = {554--571.e14},

abstract = {The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes. Autonomous activation of ISR in microglia is sufficient to induce early features of the ultrastructurally distinct "dark microglia" linked to pathological synapse loss. In AD models, microglial ISR activation exacerbates neurodegenerative pathologies and synapse loss while its inhibition ameliorates them. Mechanistically, we present evidence that ISR activation promotes the secretion of toxic lipids by microglia, impairing neuron homeostasis and survival in vitro. Accordingly, pharmacological inhibition of ISR or lipid synthesis mitigates synapse loss in AD models. Our results demonstrate that microglial ISR activation represents a neurodegenerative phenotype, which may be sustained, at least in part, by the secretion of toxic lipids.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40083800,

title = {Enhanced spectral resolution and reduced acquisition time in fiber-based wavelength-swept source Raman spectroscopy},

author = {Elahe Parham and Maxime Tousignant-Tremblay and Mireille Quémener and Martin Parent and Daniel C Côté},

doi = {10.1117/1.NPh.12.1.015014},

issn = {2329-423X},

year  = {2025},

date = {2025-01-01},

journal = {Neurophotonics},

volume = {12},

number = {1},

pages = {015014},

abstract = {SIGNIFICANCE: We introduce a fast Raman spectroscopy (SSRS) system that reduces acquisition time and enhances data quality, providing a breakthrough in SSRS for real-time applications. We demonstrate its utility in differentiating brain tissue regions based on lipid and protein content.nnAIM: Our primary goal was to develop a fast SSRS system that enables rapid data acquisition for  applications. We aimed to investigate its effectiveness in differentiating brain tissue types by analyzing lipid and protein content, ultimately enhancing classification accuracy and supporting advancements in medical diagnostics.nnAPPROACH: We implemented an optimized circuit and signal processing technique to reduce high-frequency noise and improve signal-to-noise ratio. Brain tissue measurements were validated against staining models, and classification accuracy was tested with principal component analysis (PCA) and support vector machine (SVM).nnRESULTS: Our SSRS system captures spectra in 1 s which is significantly faster than similar systems. This rapid method enables real-time monitoring and accurate classification of brain regions based on lipid-protein content, confirmed by neurofilament and Nissl staining correlations (  and 0.55, respectively). Tissue classification showed 80.20% accuracy using spectral intensity at the wavenumbers associated with C-H,  , and  vibrations and 81.23% accuracy using PCA-derived features (PC1, PC2, and PC3).nnCONCLUSIONS: The fast-SSRS system marks a significant advance in Raman spectroscopy, improving speed and data quality. Our setup captures finer spectral details, facilitating reliable differentiation of tissue types, as verified by staining methods and PCA. This method shows promise for real-time tissue analysis and medical diagnostics, outperforming traditional Raman techniques in speed and data throughput.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}