Publications by authors named "Marc Dhenain"

The amyloid cascade hypothesis assumes that the development of Alzheimer's disease (AD) is driven by a self-perpetuating cycle, in which β-amyloid (Aβ) accumulation leads to Tau pathology and neuronal damages. A particular mutation (A673T) of the amyloid precursor protein (APP) was identified among Icelandic population. It provides a protective effect against Alzheimer- and age-related cognitive decline.

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Non-human primates are a critical species for the identification of key biological mechanisms in normal and pathological aging. One of these primates, the mouse lemur, has been widely studied as a model of cerebral aging or Alzheimer's disease. The amplitude of low-frequency fluctuations of blood oxygenation level-dependent (BOLD) can be measured with functional MRI.

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Alzheimer's disease (AD) is characterized by intracerebral deposition of abnormal proteinaceous assemblies made of amyloid-β (Aß) peptides or tau proteins. These peptides and proteins induce synaptic dysfunctions that are strongly correlated with cognitive decline. Intracerebral infusion of well-defined Aβ seeds from non-mutated Aβ or Aβ peptides can increase Aβ depositions several months after the infusion.

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Article Synopsis
  • * It introduces StandardRat, a standardized fMRI acquisition protocol for rats that has been tested across 20 research centers to enhance data integration.
  • * The standardized protocol and processing pipeline improve the reliability of detecting functional connectivity patterns and are made publicly available to foster collaboration in the neuroimaging field.
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Circulating microRNAs (miRNAs) have aroused a lot of interest as reliable blood diagnostic biomarkers of Alzheimer's disease (AD). Here, we investigated the panel of expressed blood miRNAs in response to aggregated Aβ peptides infused in the hippocampus of adult rats to mimic events of the early onset of non-familial AD disorder. Aβ peptides in the hippocampus led to cognitive impairments associated with an astrogliosis and downregulation of circulating miRNA-146a-5p, -29a-3p, -29c-3p, -125b-5p, and-191-5p.

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Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e.

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The human default mode network (DMN) is engaged at rest and in cognitive states such as self-directed thoughts. Interconnected homologous cortical areas in primates constitute a network considered as the equivalent. Here, based on a cross-species comparison of the DMN between humans and non-hominoid primates (macaques, marmosets, and mouse lemurs), we report major dissimilarities in connectivity profiles.

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Article Synopsis
  • * A new imaging technique called gluCEST allows researchers to detect changes in glutamate distribution throughout the entire brain with better sensitivity and resolution compared to older methods, primarily in high-field settings.
  • * In a pioneering study, researchers explored gluCEST contrast in mouse lemur primates, finding significant age-related changes in various brain regions, paving the way for potential applications in understanding brain aging and related diseases.
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Pathogenesis of the inherited neurodegenerative disorder Huntington's disease (HD) is progressive with a long presymptomatic phase in which subtle changes occur up to 15 years before the onset of symptoms. Thus, there is a need for early, functional biomarker to better understand disease progression and to evaluate treatment efficacy far from onset. Recent studies have shown that white matter may be affected early in mutant HTT gene carriers.

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Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral Aβ angiopathy resulting in brain hemorrhages and devastating clinical impacts. Iatrogenic transmission of tau pathology is also suspected but not experimentally proven.

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The cerebral metabolic rate of oxygen consumption (CMRO) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO can be measured by direct O magnetic resonance imaging (O-MRI) of HO signal changes during inhalation of O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.

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In humans, iatrogenic transmission of cerebral amyloid-β (Aβ)-amyloidosis is suspected following inoculation of pituitary-derived hormones or dural grafts presumably contaminated with Aβ proteins as well as after cerebral surgeries. Experimentally, intracerebral inoculation of brain homogenate extracts containing misfolded Aβ can seed Aβ deposition in transgenic mouse models of amyloidosis or in non-human primates. The transmission of cerebral Aβ is governed by the host and by the inoculated samples.

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Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Characterizing neuronal networks in animals is complementary to studies in humans to understand how evolution has modelled network architecture. The mouse lemur (Microcebus murinus) is one of the smallest and more phylogenetically distant primates as compared to humans.

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Background: Masitinib is a selective tyrosine kinase inhibitor that modulates mast cells activity. A previous phase II study reported a cognitive effect of masitinib in patients with Alzheimer's disease.

Objective: We aimed to shed light on the mode of action of masitinib in Alzheimer's disease.

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Small-mammal neuroimaging offers incredible opportunities to investigate structural and functional aspects of the brain. Many tools have been developed in the last decade to analyse small animal data, but current softwares are less mature than the available tools that process human brain data. The Python package Sammba-MRI (SmAll-MaMmal BrAin MRI in Python; http://sammba-mri.

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Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons.

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Animal whole-brain functional magnetic resonance imaging (fMRI) provides a non-invasive window into brain activity. A collection of associated methods aims to replicate observations made in humans and to identify the mechanisms underlying the distributed neuronal activity in the healthy and disordered brain. Animal fMRI studies have developed rapidly over the past years, fueled by the development of resting-state fMRI connectivity and genetically encoded neuromodulatory tools.

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Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline.

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Alzheimer's disease is characterized by cognitive alterations, cerebral atrophy and neuropathological lesions including neuronal loss, accumulation of misfolded and aggregated β-amyloid peptides (Aβ) and tau proteins. Iatrogenic induction of Aβ is suspected in patients exposed to pituitary-derived hormones, dural grafts, or surgical instruments, presumably contaminated with Aβ. Induction of Aβ and tau lesions has been demonstrated in transgenic mice after contamination with Alzheimer's disease brain homogenates, with very limited functional consequences.

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Recent data confirmed the efficiency of caloric restriction for promoting both healthspan and lifespan in primates, but also revealed potential adverse effects at the central level. This paper proposes perspectives and future directions to counterbalance potential adverse effects. Efforts should be made in combining nutrition-based clinical protocols with therapeutic and/or behavioral interventions to aim for synergetic effects, and therefore delay the onset of age-related diseases without adverse effects.

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Recently developed techniques to visualize immunostained tissues in 3D and in large samples have expanded the scope of microscopic investigations at the level of the whole brain. Here, we propose to adapt voxel-based statistical analysis to 3D high-resolution images of the immunostained rodent brain. The proposed approach was first validated with a simulation dataset with known cluster locations.

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We present a dataset made of 3D digital brain templates and of an atlas of the gray mouse lemur (), a small prosimian primate of growing interest for studies of primate biology and evolution. A template image was constructed from magnetic resonance imaging (MRI) data of 34 animals. This template was then manually segmented into 40 cortical, 74 subcortical and 6 cerebro-spinal fluid (CSF) regions.

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The gray mouse lemur (Microcebus murinus) is a small prosimian of growing interest for studies of primate biology and evolution, and notably as a model organism of brain aging. As brain atlases are essential tools for brain investigation, the objective of the current work was to create the first 3D digital atlas of the mouse lemur brain. For this, a template image was constructed from in vivo magnetic resonance imaging (MRI) data of 34 animals.

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Astrocyte reactivity and neuroinflammation are hallmarks of CNS pathological conditions such as Alzheimer's disease. However, the specific role of reactive astrocytes is still debated. This controversy may stem from the fact that most strategies used to modulate astrocyte reactivity and explore its contribution to disease outcomes have only limited specificity.

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