@article{SchaanProfes2026,

title = {Autophagy Is Required for Dopaminergic Axon Development and Confers Their Responsiveness to Guidance Cues},

author = {Marcos Schaan Profes and Charles Gora and Flavie Lavoie-Cardinal and Armen Saghatelyan and Martin Lévesque},

doi = {10.1523/jneurosci.1224-25.2026},

issn = {1529-2401},

year  = {2026},

date = {2026-05-27},

journal = {J. Neurosci.},

volume = {46},

number = {21},

publisher = {Society for Neuroscience},

abstract = {Midbrain dopamine (mDA) neurons play a wide range of brain functions, but the molecular mechanisms driving the formation of mDA circuits remain largely unknown. Here, we show that autophagy, the main cellular recycling pathway, is present in the growth cones of developing mDA neurons, and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth and guidance, we knocked out essential autophagy genes (Atg12, Atg5) specifically in mDA neurons in mice of either sex. Autophagy-deficient mDA axons exhibit axonal swellings and reduced branching both in vitro and in vivo. Strikingly, deletion of autophagy-related genes completely blunted the response of mDA neurons to both chemorepulsive and chemoattractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neuron development by orchestrating axonal growth and guidance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40534558,

title = {Investigation of Poststroke Depression Following a Nucleus Accumbens Infarct in Mice},

author = {Jonathan Bouchard and Béatrice Daigle and Adeline Collignon and Vincent St-Arnault and Luisa Bandeira Binder and Laura Menegatti Bevilacqua and Véronique Rioux and Laurence Dion-Albert and Manon Lebel and Martin Lévesque and Michèle Desjardins and Caroline Ménard},

doi = {10.1161/STROKEAHA.125.050839},

issn = {1524-4628},

year  = {2025},

date = {2025-09-01},

journal = {Stroke},

volume = {56},

number = {9},

pages = {2772--2781},

abstract = {BACKGROUND: Poststroke depression (PSD) affects ≈33% of individuals 1 year after a stroke. Blood-brain barrier (BBB) dysfunction in the nucleus accumbens (NAc), a hub for emotional processing, reward, and mood regulation, has been linked to stress-induced depressive-like behaviors in male mice. Neurovascular alterations were also observed in postmortem tissue samples from men with a diagnosis of major depression. Thus, we aimed to investigate if BBB changes in the NAc could contribute to PSD pathophysiology.nnMETHODS: Stereotaxic injection of ET-1 (endothelin-1), a potent vasoconstrictor, was performed in the NAc of male mice to create a focal brain stroke, and then, infarct size and localization were assessed and quantified. We subsequently evaluated transcriptomic and morphological effects of the infarct on BBB-related genes and cells in the NAc, particularly those known to be altered after stress exposure in mice or human depression. BBB integrity was assessed with a dextran dye, and magnetic resonance imaging scans were conducted before versus after the injection of Gadovist, a contrast agent. Last, a battery of behavioral tests related to depressive- and anxiety-like behaviors was performed to determine if an infarct in the NAc is sufficient to induce a PSD-like phenotype.nnRESULTS: Following ET-1 injection, ≈50% of the total lesion was observed in the NAc leading to BBB hyperpermeability in this brain area. BBB gene expression was impacted by ET-1, and also surgery alone and profiles were differentially regulated throughout time up to 14 days. Gliosis in the NAc was observed with increased reactivity of astrocytes and microglia. The effect of ET-1 on PSD-like symptoms was limited. However, body weight, sociability, and activity were affected by surgery with a more pronounced impact of ET-1 on social interactions compared with naive animals.nnCONCLUSIONS: While no clear PSD phenotype was observed following an ET-1-induced stroke in the NAc of male mice, our study shed light on the technical complexity of focal lesions in deep brain structures, an understudied phenomenon occurring in humans. We provide technical insights for the development of a mouse model of deep brain lesions, characterize its impact at molecular, cellular, and behavioral levels, and highlight the need to control for vascular alterations when performing stroke surgeries.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40530583,

title = {Enhancing the diagnostic potential of electroretinography in Parkinson's disease: A review of protocol and cohort criteria},

author = {Victoria Soto Linan and Marc Hébert and Martin Lévesque},

doi = {10.1177/1877718X251331863},

issn = {1877-718X},

year  = {2025},

date = {2025-06-01},

journal = {J Parkinsons Dis},

volume = {15},

number = {4},

pages = {694--709},

abstract = {Electroretinography has emerged as a promising tool for identifying retinal functional anomalies in major psychiatric and neurodevelopmental disorders, such as schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder, positioning it as a potential biomarker of monoaminergic dysfunction. However, despite its potential, electroretinography studies in Parkinson's disease (PD) over the past decades have been inconsistent, largely due to variations in research methodologies. These limitations diminish its potential and hinder the association between retinal electrophysiological responses and PD neuropathology. To address this challenge, this review examines the most relevant sources of data variability and reduced reproducibility in electroretinography studies aimed at detecting a retinal functional signature characteristic of PD. We propose the consolidation of four key protocol factors and five cohort criteria to enhance the diagnostic accuracy of electroretinography in PD biomarker research. As electroretinography protocols are adapted from their clinical origins for research purposes, we argue that careful attention must be given to electrode type and placement, as well as to factors like age, sex, disease duration and severity, medication intake, psychiatric conditions, and comorbidities in cohort selection to ensure reproducible results. Suggesting that past inconsistencies in these areas may explain the variability in reported results and contribute to the lack of consensus on which electroretinography parameters comprise a disease signature in PD, we ultimately offer recommendations to improve the utility of electroretinography techniques as early biomarkers for PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40090470,

title = {Early detection of Parkinson's disease: Retinal functional impairments as potential biomarkers},

author = {Victoria Soto Linan and Véronique Rioux and Modesto Peralta and Nicolas Dupré and Marc Hébert and Martin Lévesque},

doi = {10.1016/j.nbd.2025.106872},

issn = {1095-953X},

year  = {2025},

date = {2025-05-01},

journal = {Neurobiol Dis},

volume = {208},

pages = {106872},

abstract = {BACKGROUND: Parkinson's disease is typically diagnosed after substantial neurodegeneration despite early non-motor symptoms manifesting decades earlier. These changes offer a promising avenue for diagnostic exploration, especially within the eye, which has been proposed as a "window to the brain."nnOBJECTIVE: The aim was to identify biomarkers by validating the use of electroretinography, a non-invasive technique, to detect early retinal function anomalies reflecting central dysfunction.nnMETHODS: Homozygous M83 transgenic mice (n = 10 males, 11 females), overexpressing human A53T α-synuclein, underwent behavioral tests and electroretinography measurements. Histological evaluation was performed at four months to analyze synucleinopathies and neurodegeneration. Electroretinography was also conducted with idiopathic PD patients (mean age 63.35 ± 7.73; disease duration 4.15 ± 2.06; H&Y score 2.07 ± 0.59; n = 12 males, 8 females) and healthy age-matched controls (mean age 61.65 ± 8.39; n = 9 males, 11 females).nnRESULTS: Rodent electroretinography revealed reduced photopic b-wave, PhNR b-wave, and PhNR-wave amplitudes at two and four months, particularly in females, indicating bipolar and retinal ganglion cell impairment. Based on retinal histological assessment, these changes might arise from α-synuclein pathology occurring in outer retinal layers. Likewise, the scotopic b-wave and PhNR waveform were similarly impaired in female participants with Parkinson's disease. The scotopic oscillatory potentials isolated further identified an attenuated amacrine cell output in females.nnCONCLUSIONS: Findings from both mice and human cohorts indicate that retinal functional impairments can be detected early in the progression of Parkinson's disease, particularly among females. These tools show promise in facilitating early diagnosis, disease monitoring, therapeutic intervention, and ultimately enhancing patient outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38852127,

title = {The laminar position, morphology, and gene expression profiles of cortical astrocytes are influenced by time of birth from ventricular/subventricular progenitors},

author = {Daniela Lozano Casasbuenas and Ines Kortebi and Charles Gora and Erica Y Scott and Celeste Gomes and Markley Silva Oliveira and Tanvi Sharma and Emerson Daniele and Arman Olfat and Rachel Gibbs and Scott A Yuzwa and Emily A Gilbert and Patrick Küry and Aaron R Wheeler and Martin Lévesque and Maryam Faiz},

doi = {10.1002/glia.24578},

issn = {1098-1136},

year  = {2024},

date = {2024-09-01},

journal = {Glia},

volume = {72},

number = {9},

pages = {1693--1706},

abstract = {Astrocytes that reside in superficial (SL) and deep cortical layers have distinct molecular profiles and morphologies, which may underlie specific functions. Here, we demonstrate that the production of SL and deep layer (DL) astrocyte populations from neural progenitor cells in the mouse is temporally regulated. Lineage tracking following in utero and postnatal electroporation with PiggyBac (PB) EGFP and birth dating with EdU and FlashTag, showed that apical progenitors produce astrocytes during late embryogenesis (E16.5) that are biased to the SL, while postnatally labeled (P0) astrocytes are biased to the DL. In contrast, astrocytes born during the predominantly neurogenic window (E14.5) showed a random distribution in the SL and DL. Of interest, E13.5 astrocytes birth dated at E13.5 with EdU showed a lower layer bias, while FT labeling of apical progenitors showed no bias. Finally, examination of the morphologies of "biased" E16.5- and P0-labeled astrocytes demonstrated that E16.5-labeled astrocytes exhibit different morphologies in different layers, while P0-labeled astrocytes do not. Differences based on time of birth are also observed in the molecular profiles of E16.5 versus P0-labeled astrocytes. Altogether, these results suggest that the morphological, molecular, and positional diversity of cortical astrocytes is related to their time of birth from ventricular/subventricular zone progenitors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37766924,

title = {Shining light on the noradrenergic system},

author = {Emmeraude Tanguay and Sarah-Julie Bouchard and Martin Lévesque and Paul De Koninck and Vincent Breton-Provencher},

doi = {10.1117/1.NPh.10.4.044406},

issn = {2329-423X},

year  = {2023},

date = {2023-10-01},

journal = {Neurophotonics},

volume = {10},

number = {4},

pages = {044406},

abstract = {Despite decades of research on the noradrenergic system, our understanding of its impact on brain function and behavior remains incomplete. Traditional recording techniques are challenging to implement for investigating  noradrenergic activity, due to the relatively small size and the position in the brain of the locus coeruleus (LC), the primary location for noradrenergic neurons. However, recent advances in optical and fluorescent methods have enabled researchers to study the LC more effectively. Use of genetically encoded calcium indicators to image the activity of noradrenergic neurons and biosensors that monitor noradrenaline release with fluorescence can be an indispensable tool for studying noradrenergic activity. In this review, we examine how these methods are being applied to record the noradrenergic system in the rodent brain during behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37468944,

title = {Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions},

author = {Axelle Dovonou and Cyril Bolduc and Victoria Soto Linan and Charles Gora and Modesto R Peralta Iii and Martin Lévesque},

doi = {10.1186/s40035-023-00368-8},

issn = {2047-9158},

year  = {2023},

date = {2023-07-01},

journal = {Transl Neurodegener},

volume = {12},

number = {1},

pages = {36},

abstract = {Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains a serious affliction that affects a growing proportion of the population. Prevailing treatments only alleviate symptoms; there is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease. Over the past decades, several animal models have been developed to study PD. Although no model precisely recapitulates the pathology, they still provide valuable information that contributes to our understanding of the disease and the limitations of our treatment options. This review comprehensively summarizes the different animal models available for Parkinson's research, with a focus on those induced by drugs, neurotoxins, pesticides, genetic alterations, α-synuclein inoculation, and viral vector injections. We highlight their characteristics and ability to reproduce PD-like phenotypes. It is essential to realize that the strengths and weaknesses of each model and the induction technique at our disposal are determined by the research question being asked. Our review, therefore, seeks to better aid researchers by ensuring a concrete discernment of classical and novel animal models in PD research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37362387,

title = {Millimetric scale two-photon Bessel-Gauss beam light sheet microscopy with three-axis isotropic resolution using an axicon lens},

author = {Cléophace Akitegetse and Thomas Charland and Mireille Quémener and Charles Gora and Véronique Rioux and Michel Piché and Yves De Koninck and Martin Lévesque and Daniel C Côté},

doi = {10.1117/1.NPh.10.3.035002},

issn = {2329-423X},

year  = {2023},

date = {2023-07-01},

journal = {Neurophotonics},

volume = {10},

number = {3},

pages = {035002},

abstract = {SIGNIFICANCE: Typical light sheet microscopes suffer from artifacts related to the geometry of the light sheet. One main inconvenience is the non-uniform thickness of the light sheet obtained with a Gaussian laser beam.nnAIM: We developed a two-photon light sheet microscope that takes advantage of a thin and long Bessel-Gauss beam illumination to increase the sheet extent without compromising the resolution.nnAPPROACH: We use an axicon lens placed directly at the output of an amplified femtosecond laser to produce a long Bessel-Gauss beam on the sample. We studied the dopaminergic system and its projections in a whole cleared mouse brain.nnRESULTS: Our light sheet microscope allows an isotropic resolution of  in all three axes of the scanned volume while keeping a millimetric-sized field of view, and a fast acquisition rate of up to . With slight modifications to the optical setup, the sheet extent can be increased to 6 mm.nnCONCLUSION: The proposed system's sheet extent and resolution surpass currently available systems, enabling the fast imaging of large specimens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36973269,

title = {The small GTPase Rit2 modulates LRRK2 kinase activity, is required for lysosomal function and protects against alpha-synuclein neuropathology},

author = {Julia Obergasteiger and Anne-Marie Castonguay and Sara Pizzi and Stefano Magnabosco and Giulia Frapporti and Evy Lobbestael and Veerle Baekelandt and Andrew A Hicks and Peter P Pramstaller and Claude Gravel and Corrado Corti and Martin Lévesque and Mattia Volta},

doi = {10.1038/s41531-023-00484-2},

issn = {2373-8057},

year  = {2023},

date = {2023-03-01},

journal = {NPJ Parkinsons Dis},

volume = {9},

number = {1},

pages = {44},

abstract = {In Parkinson's disease (PD) misfolded alpha-synuclein (aSyn) accumulates in the substantia nigra, where dopaminergic neurons are progressively lost. The mechanisms underlying aSyn pathology are still unclear, but they are hypothesized to involve the autophagy-lysosome pathway (ALP). LRRK2 mutations are a major cause of familial and sporadic PD, and LRRK2 kinase activity has been shown to be involved in pS129-aSyn inclusion modulation. We observed selective downregulation of the novel PD risk factor RIT2 in vitro and in vivo. Rit2 overexpression in G2019S-LRRK2 cells rescued ALP abnormalities and diminished aSyn inclusions. In vivo, viral mediated overexpression of Rit2 operated neuroprotection against AAV-A53T-aSyn. Furthermore, Rit2 overexpression prevented the A53T-aSyn-dependent increase of LRRK2 kinase activity in vivo. On the other hand, reduction of Rit2 levels leads to defects in the ALP, similar to those induced by the G2019S-LRRK2 mutation. Our data indicate that Rit2 is required for correct lysosome function, inhibits overactive LRRK2 to ameliorate ALP impairment, and counteracts aSyn aggregation and related deficits. Targeting Rit2 could represent an effective strategy to combat neuropathology in familial and idiopathic PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35263320,

title = {A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease},

author = {Morgan Bérard and Razan Sheta and Sarah Malvaut and Raquel Rodriguez-Aller and Maxime Teixeira and Walid Idi and Roxanne Turmel and Melanie Alpaugh and Marilyn Dubois and Manel Dahmene and Charleen Salesse and Jérôme Lamontagne-Proulx and Marie-Kim St-Pierre and Omid Tavassoly and Wen Luo and Esther Del Cid-Pellitero and Raza Qazi and Jae-Woong Jeong and Thomas M Durcan and Luc Vallières and Marie-Eve Tremblay and Denis Soulet and Martin Lévesque and Francesca Cicchetti and Edward A Fon and Armen Saghatelyan and Abid Oueslati},

doi = {10.1371/journal.pbio.3001578},

issn = {1545-7885},

year  = {2022},

date = {2022-03-01},

journal = {PLoS Biol},

volume = {20},

number = {3},

pages = {e3001578},

abstract = {Neurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, the exact role of protein aggregation in the pathophysiology of these disorders remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of protein aggregation, and the investigation of early dynamic events associated with inclusion formation. Here, we report on the development of a light-inducible protein aggregation (LIPA) system that enables spatiotemporal control of α-synuclein (α-syn) aggregation into insoluble deposits called Lewy bodies (LBs), the pathological hallmark of Parkinson disease (PD) and other proteinopathies. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical, and ultrastructural features of authentic LBs observed in PD-diseased brains. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration and PD-like motor impairments. Collectively, our findings provide a new tool for the generation, visualization, and dissection of the role of α-syn aggregation in PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}