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Article ; Online: Association of Cumulative Lifetime Exposure to Female Hormones With Cerebral Small Vessel Disease in Postmenopausal Women in the UK Biobank.

Cote, Samantha / Perron, Thomas-Louis / Baillargeon, Jean-Patrice / Bocti, Christian / Lepage, Jean-Francois / Whittingstall, Kevin

Neurology

2023 Volume 101, Issue 20, Page(s) e1970–e1978

Abstract: Background and objectives: Rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones. It remains unknown whether the cumulative exposure to hormones across a female person's premenopausal life ... ...

Abstract	Background and objectives: Rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones. It remains unknown whether the cumulative exposure to hormones across a female person's premenopausal life extends the window of cerebrovascular protection to the postmenopausal period. To investigate this, we examined the relationship between lifetime hormone exposure (LHE) and cerebral small vessel disease in more than 9,000 postmenopausal women in the UK-Biobank. Methods: The cohort consisted of women (aged 40-69 years) who attended one of 22 research centers across the United Kingdom between 2006 and 2010. Women were excluded if they were premenopausal when scanned, had missing reproductive history data, self-reported neurologic disorders, brain cancer, cerebral vascular incidents, head or neurologic injury, and nervous system infection. Endogenous LHE (LHE Results: A total of 9,163 postmenopausal women (age 64.21 ± 6.81 years) were retained for analysis. Average LHE Discussion: Women with more prolonged exposure to endogenous hormones show relatively smaller burden of cerebral small vessel disease independent of the history of oral contraceptive use or hormone replacement therapy. Our results highlight the critical role endogenous hormones play in female brain health and provide real-world evidence of the protective effects premenopausal endogenous hormone exposure plays on postmenopausal cerebrovascular health.
MeSH term(s)	Pregnancy ; Humans ; Female ; Postmenopause ; Risk Factors ; Biological Specimen Banks ; Menopause ; Cerebral Small Vessel Diseases/diagnostic imaging ; Cerebral Small Vessel Diseases/epidemiology ; Hormones
Chemical Substances	Hormones
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000207845
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Article ; Online: Indicateurs biologiques et méthodes d’évaluation pour la directive cadre européenne sur l'eau

CHAUVIN, Christian / LEPAGE, Mario

Sciences, Eaux & Territoires, Vol 2021, Iss 37, Pp 22-

un contexte cadré, des approches novatrices, des enjeux essentiels

2021 Volume 29

Abstract: La directive cadre européenne sur l’eau a placé l’hydrobiologie au cœur de l’évaluation de la qualité des milieux aquatiques. Dans ce contexte, la bioindication est redevenue une discipline très active de l’écologie, soutenue par des enjeux sociétaux ... ...

Abstract	La directive cadre européenne sur l’eau a placé l’hydrobiologie au cœur de l’évaluation de la qualité des milieux aquatiques. Dans ce contexte, la bioindication est redevenue une discipline très active de l’écologie, soutenue par des enjeux sociétaux forts. Dans cet article, les auteurs présentent un aperçu des différents aspects du contexte dans lequel les indicateurs biologiques et les méthodes d’évaluation ont été développés, principalement pour les cours d’eau et les estuaires. Ils montrent au-delà les enjeux auxquels ces travaux doivent faire face.
Keywords	indicateur biologique ; évaluation environnementale ; directive cadre européenne sur l'eau ; méthode ; Environmental technology. Sanitary engineering ; TD1-1066 ; Environmental sciences ; GE1-350
Language	French
Publishing date	2021-12-01T00:00:00Z
Publisher	Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE)
Document type	Article ; Online
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Article ; Online: Development and validation of a highly specific in-house chemiluminescent-based serological assay for the detection of antibodies directed against the human monkeypox virus.

Therrien, Christian / Prévost, Jérémie / Blais, Antoine Cloutier / Turcotte, Sonia / Gendron-Lepage, Gabrielle / Finzi, Andrés / Fafard, Judith

Journal of virological methods

2023 Volume 322, Page(s) 114836

MeSH term(s)	Humans ; Monkeypox virus ; Antibodies ; Mpox (monkeypox)/diagnosis
Chemical Substances	Antibodies
Language	English
Publishing date	2023-10-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2023.114836
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Article: Expression of exogenous mRNAs to study gene function in echinoderm embryos.

Molina, Maria Dolores / Gache, Christian / Lepage, Thierry

Methods in cell biology

2019 Volume 151, Page(s) 239–282

Abstract: With the completion of the genome sequencing projects, a new challenge for developmental biologists is to assign a function to the thousands of genes identified. Expression of exogenous mRNAs is a powerful, versatile and rapid technique that can be used ... ...

Abstract	With the completion of the genome sequencing projects, a new challenge for developmental biologists is to assign a function to the thousands of genes identified. Expression of exogenous mRNAs is a powerful, versatile and rapid technique that can be used to study gene function during development of the sea urchin. This chapter describes how this technique can be used to analyze gene function in echinoderm embryos, how it can be combined with cell transplantation to perform mosaic analysis and how it can be applied to identify downstream targets genes of transcription factors and signaling pathways. We describe specific examples of the use of overexpression of mRNA to analyze gene function, mention the benefits and current limitations of the technique and emphasize the importance of using different controls to assess the specificity of the effects observed. Finally, this chapter details the different steps, vectors and protocols for in vitro production of mRNA and phenotypic analysis.
MeSH term(s)	Animals ; Embryo, Nonmammalian ; Gene Expression Regulation, Developmental/genetics ; Gene Regulatory Networks/genetics ; Genomics/methods ; RNA, Messenger/genetics ; Sea Urchins/genetics ; Sea Urchins/growth & development ; Signal Transduction/genetics ; Transcription Factors/genetics
Chemical Substances	RNA, Messenger ; Transcription Factors
Language	English
Publishing date	2019-01-02
Publishing country	United States
Document type	Journal Article ; Review
ISSN	0091-679X
ISSN	0091-679X
DOI	10.1016/bs.mcb.2018.10.011
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Article ; Online: White matter microstructural variability linked to differential attentional skills and impulsive behavior in a pediatric population.

Gagnon, Anthony / Grenier, Gabrielle / Bocti, Christian / Gillet, Virginie / Lepage, Jean-François / Baccarelli, Andrea A / Posner, Jonathan / Descoteaux, Maxime / Takser, Larissa

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 33, Issue 5, Page(s) 1895–1912

Abstract: Structural and functional magnetic resonance imaging (MRI) studies have suggested a neuroanatomical basis that may underly attention-deficit-hyperactivity disorder (ADHD), but the anatomical ground truth remains unknown. In addition, the role of the ... ...

Abstract	Structural and functional magnetic resonance imaging (MRI) studies have suggested a neuroanatomical basis that may underly attention-deficit-hyperactivity disorder (ADHD), but the anatomical ground truth remains unknown. In addition, the role of the white matter (WM) microstructure related to attention and impulsivity in a general pediatric population is still not well understood. Using a state-of-the-art structural connectivity pipeline based on the Brainnetome atlas extracting WM connections and its subsections, we applied dimensionality reduction techniques to obtain biologically interpretable WM measures. We selected the top 10 connections-of-interests (located in frontal, parietal, occipital, and basal ganglia regions) with robust anatomical and statistical criteria. We correlated WM measures with psychometric test metrics (Conner's Continuous Performance Test 3) in 171 children (27 Dx ADHD, 3Dx ASD, 9-13 years old) from the population-based GESTation and Environment cohort. We found that children with lower microstructural complexity and lower axonal density show a higher impulsive behavior on these connections. When segmenting each connection in subsections, we report WM alterations localized in one or both endpoints reflecting a specific localization of WM alterations along each connection. These results provide new insight in understanding the neurophysiology of attention and impulsivity in a general population.
MeSH term(s)	Humans ; Child ; Adolescent ; White Matter/pathology ; Impulsive Behavior ; Magnetic Resonance Imaging ; Basal Ganglia ; Attention Deficit Disorder with Hyperactivity ; Attention/physiology ; Brain
Language	English
Publishing date	2022-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhac180
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Article ; Online: Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans.

Remahi, Sarah / Mabika, Madora / Côté, Samantha / Iorio-Morin, Christian / Near, Jamie / Hui, Steve C N / Edden, Richard A E / Théoret, Hugo / Whittingstall, Kevin / Lepage, Jean-François

Progress in neuro-psychopharmacology & biological psychiatry

2023 Volume 129, Page(s) 110892

Abstract: Background: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant ... ...

Abstract	Background: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. Objective/hypothesis: The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. Methods: We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). Results: Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. Conclusions: Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.
MeSH term(s)	Adult ; Humans ; Motor Cortex/diagnostic imaging ; Motor Cortex/physiology ; Neural Inhibition/physiology ; Evoked Potentials, Motor/physiology ; Glutamic Acid/metabolism ; Transcranial Magnetic Stimulation/methods ; Basal Ganglia/diagnostic imaging ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	781181-0
ISSN	1878-4216 ; 0278-5846
ISSN (online)	1878-4216
ISSN	0278-5846
DOI	10.1016/j.pnpbp.2023.110892
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Article: Trans-disciplinary diagnosis for an in-depth reform of regulatory expertise in the field of environmental toxicology and security.

Spiroux de Vendômois, Joël / Bourdineaud, Jean-Paul / Apoteker, Arnaud / Defarge, Nicolas / Gaillard, Emilie / Lepage, Corinne / Testart, Jacques / Vélot, Christian

Toxicological research

2021 Volume 37, Issue 4, Page(s) 405–419

Abstract: Repeated health and environmental scandals, the loss of biodiversity and the recent burst of chronic diseases constantly remind us the inability of public authorities and risk assessment agencies to protect health and the environment. After reviewing the ...

Abstract	Repeated health and environmental scandals, the loss of biodiversity and the recent burst of chronic diseases constantly remind us the inability of public authorities and risk assessment agencies to protect health and the environment. After reviewing the main shortcomings of our evaluation system of chemicals and new technologies, supported by some concrete examples, we develop a number of proposals to reform both the risk assessment agencies and the evaluation processes. We especially propose the establishment of an independent structure, a High Authority of Expertise, supervising, either at European level or at national level, all the evaluation agencies, and ensuring the transparency, the methodology and the deontology of the expertise. In addition to modifying the evaluation protocols, both in their nature and in their content, especially in order to adapt them to current pollutants such as endocrine disruptors, we propose a reform of the expertise processes based on transparency, contradiction, and greater democracy, including close collaboration between the institutional and scientific parties on the one hand and the whole civil society on the other. All the proposals we make are inspired by the desire to prevent, through appropriate mechanisms, the human, health, ecological, but also economic consequences of contemporary technological choices.
Language	English
Publishing date	2021-01-25
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2727978-9
ISSN	2234-2753 ; 1976-8257
ISSN (online)	2234-2753
ISSN	1976-8257
DOI	10.1007/s43188-020-00075-w
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Article ; Online: Microstructural abnormalities in deep and superficial white matter in youths with mild traumatic brain injury.

Stojanovski, Sonja / Nazeri, Arash / Lepage, Christian / Ameis, Stephanie / Voineskos, Aristotle N / Wheeler, Anne L

NeuroImage. Clinical

2019 Volume 24, Page(s) 102102

Abstract: Background: Diffusion Tensor Imaging (DTI) studies of traumatic brain injury (TBI) have focused on alterations in microstructural features of deep white matter fibers (DWM), though post-mortem studies have demonstrated that injured axons are often ... ...

Abstract	Background: Diffusion Tensor Imaging (DTI) studies of traumatic brain injury (TBI) have focused on alterations in microstructural features of deep white matter fibers (DWM), though post-mortem studies have demonstrated that injured axons are often observed at the gray-white matter interface where superficial white matter fibers (SWM) mediate local connectivity. Objectives: To examine microstructural alterations in SWM and DWM in youths with a history of mild TBI and examine the relationship between white matter alterations and attention. Methods: Using DTIDWM fractional anisotropy (FA) and SWM FA in youths with mild TBI (TBI, n=63) were compared to typically developing and psychopathology matched control groups (n=63 each). Following tract-based spatial statistics, SWM FA was assessed by applying a probabilistic tractography derived SWM mask, and DWM FA was captured with a white matter fiber tract mask. Voxel-wise z-score calculations were used to derive a count of voxels with abnormally high and low FA for each participant. Analyses examined DWM and SWM FA differences between TBI and control groups, the relationship between attention and DWM and SWM FA and the relative susceptibility of SWM compared to DWM FA to alterations associated with mild TBI. Results: Case-based comparisons revealed more voxels with low FA and fewer voxels with high FA in SWM in youths with mild TBI compared to both control groups. Equivalent comparisons in DWM revealed a similar pattern of results, however, no group differences for low FA in DWM were found between mild TBI and the control group with matched psychopathology. Slower processing speed on the attention task was correlated with the number of voxels with low FA in SWM in youths with mild TBI. Conclusions: Within a sample of youths with a history of mild TBI, this study identified abnormalities in SWM microstructure associated with processing speed. The majority of DTI studies of TBI have focused on long-range DWM fiber tracts, often overlooking the SWM fiber type.
MeSH term(s)	Adolescent ; Anisotropy ; Attention ; Brain Concussion/diagnostic imaging ; Brain Concussion/physiopathology ; Brain Concussion/psychology ; Case-Control Studies ; Child ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; Female ; Humans ; Image Processing, Computer-Assisted ; Male ; Reaction Time ; White Matter/diagnostic imaging ; Young Adult
Language	English
Publishing date	2019-11-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2019.102102
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Article ; Online: Microstructural abnormalities in deep and superficial white matter in youths with mild traumatic brain injury

Sonja Stojanovski / Arash Nazeri / Christian Lepage / Stephanie Ameis / Aristotle N. Voineskos / Anne L. Wheeler

NeuroImage: Clinical, Vol 24, Iss , Pp - (2019)

2019

Abstract	Background: Diffusion Tensor Imaging (DTI) studies of traumatic brain injury (TBI) have focused on alterations in microstructural features of deep white matter fibers (DWM), though post-mortem studies have demonstrated that injured axons are often observed at the gray-white matter interface where superficial white matter fibers (SWM) mediate local connectivity. Objectives: To examine microstructural alterations in SWM and DWM in youths with a history of mild TBI and examine the relationship between white matter alterations and attention. Methods: Using DTIDWM fractional anisotropy (FA) and SWM FA in youths with mild TBI (TBI, n=63) were compared to typically developing and psychopathology matched control groups (n=63 each). Following tract-based spatial statistics, SWM FA was assessed by applying a probabilistic tractography derived SWM mask, and DWM FA was captured with a white matter fiber tract mask. Voxel-wise z-score calculations were used to derive a count of voxels with abnormally high and low FA for each participant. Analyses examined DWM and SWM FA differences between TBI and control groups, the relationship between attention and DWM and SWM FA and the relative susceptibility of SWM compared to DWM FA to alterations associated with mild TBI. Results: Case-based comparisons revealed more voxels with low FA and fewer voxels with high FA in SWM in youths with mild TBI compared to both control groups. Equivalent comparisons in DWM revealed a similar pattern of results, however, no group differences for low FA in DWM were found between mild TBI and the control group with matched psychopathology. Slower processing speed on the attention task was correlated with the number of voxels with low FA in SWM in youths with mild TBI. Conclusions: Within a sample of youths with a history of mild TBI, this study identified abnormalities in SWM microstructure associated with processing speed. The majority of DTI studies of TBI have focused on long-range DWM fiber tracts, often overlooking the SWM fiber type. Keywords: Mild traumatic brain injury, Superficial white matter, Diffusion tensor imaging, Processing speed
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	150
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease.

Croteau, Etienne / Castellano, Christian-Alexandre / Richard, Marie Anne / Fortier, Mélanie / Nugent, Scott / Lepage, Martin / Duchesne, Simon / Whittingstall, Kevin / Turcotte, Éric E / Bocti, Christian / Fülöp, Tamàs / Cunnane, Stephen C

Journal of Alzheimer's disease : JAD

2018 Volume 64, Issue 2, Page(s) 551–561

Abstract: Background: In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement.: Objective: To assess whether brain ketone uptake in AD increases ...

Abstract	Background: In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement. Objective: To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults. Methods: Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention. Results: Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization. Conclusion: Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.
MeSH term(s)	Acetates/metabolism ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/diet therapy ; Alzheimer Disease/pathology ; Brain/diagnostic imaging ; Brain/metabolism ; Carbon/metabolism ; Energy Metabolism/physiology ; Female ; Fluorodeoxyglucose F18/metabolism ; Humans ; Ketones/blood ; Magnetic Resonance Imaging ; Male ; Positron-Emission Tomography ; Triglycerides/therapeutic use
Chemical Substances	Acetates ; Ketones ; Triglycerides ; carbon-11 acetate ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Carbon (7440-44-0)
Language	English
Publishing date	2018-04-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-180202
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