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Mechanisms for regulating brain macrophages in central nervous system diseases
Le but de ce travail était de mieux comprendre les mécanismes de régulation influençant le recrutement des macrophages cérébraux et leur activation dans différentes affections du système nerveux central. À cette fin, trois objectifs ont été définis : (1) Mettre en évidence le rôle du TNF dans l'infi...
Ultrastructural characterization of the dark microglia across contexts of health, disease, and stages of lifespan
Microglia are the principle neuroimmune cells of the brain, having important roles both in brain homeostasis as well as pathological states. Apart from the secretion of pro-inflammatory or anti-inflammatory molecules, they also participate directly at the synaptic level in the remodeling of neuronal...
Study of microglie in marred monkeys with MPTP as a model of Parkinson’s disease: effect of treatment with levodopa
Microglia are the brain immune cells which exert crucial physiological roles across the lifespan. To assess whether their functions are impaired in the pathophysiology of Parkinson disease (PD), the most common neurodegenerative motor disorder, we characterized their changes in density, morphology,...
Super-resolution STED and two-photon microscopy of dendritic spine and microglial dynamics
Activity-dependent changes in neuronal connectivity are thought to underlie learning and memory. I developed and applied novel high-resolution imaging-based approaches to study (i) microglia-spine interactions and (ii) the turnover of dendritic spines in the mouse hippocampus, which are both thought...
Role of myeloid cells in murine neuroinflammation models
Inflammation of the central nervous system (CNS), known as neuroinflammation, is a hallmark of chronic neurodegenerative diseases such as multiple sclerosis (MS) and Alzheimer’s disease (AD). Detailed characterization of each cell population and its specific molecular signature in different patholog...
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Study of the blood-brain interface and glial cells during sepsis-associated encephalopathy : from imaging to histology
Sepsis-associated encephalopathy (SAE) refers to central nervous system dysfunction during the systemic inflammatory response to infection. In septic patients with encephalopathy MRI has indicated both gray and white matter abnormalities that were associated with worse cognitive outcome including de...
Effects of phthalates, environmental endocrine disrupting chemicals, on the neurovascular unit in adult male mouse
Adult male mice exposure to low doses of ubiquitous endocrine disruptors of phthalate family, DEHP, induces alteration of neural function and of behaviors due to down-regulation of androgen receptors (AR). The link between reduced androgen sensitivity, neurovascular unit (NVU) dysfunction and neuroi...
Neuroinflammation and neuroprotection in Parkinson's disease animal model mimicking the early stages of the disease (6-hydroxydopamine lesion in rat)
Currently, therapeutic strategies in Parkinson’s disease are symptomatic and the progression of the disease is uncontrolled, requiring the development of new neuroprotective approaches. Neuroinflammation plays a major role in the neurodegenerative process where it occurs early through the activation...
Microglial and BDNF impact on the induction of the post ischemic neuroplasticity
Evidences showing that under certain circumstances, inflammatory response could be neuroprotective and could also promote adult neurogenesis are growing. In this context, the objective of this work was to investigate the impact of microglial cells in the neuroplastic events. Rats were subjected to p...
Brain perivascular macrophages as modulators of the post-ischemic inflammatory response
Schemic stroke is one of the main causes of death and permanent disability worldwide. Stroke-induced inflammatory processes, including the activation of resident glial cells as well as the invasion of circulating leukocytes, have been proposed as key contributors of the ischemic stroke pathophysiolo...
Evolution of corticospinal tract integrity in stroked marmoset monkeys : Towards a bioimplant and stem cell therapeutic strategy
Ischemic stroke frequently damages brain regions involved in the control of voluntary movement and remains a leading cause of adult-acquired disability. Although hundreds of therapeutic strategies have shown potential benefits in animal models of stroke, motor rehabilitation and physiotherapy remain...
Elucidating molecular mechanisms of post operative pain chronicization
Chronic pain caused by surgical procedures (CPSP) remains a significant clinical problem that seriously impacts postoperative rehabilitation and health-related quality of life. Existing treatments are outdated and ineffective over the long term. For these reasons, CPSP has grown into a health priori...
Inactivation of peroxisomal ABC transporters, ABCD1 and ABCD2 in BV-2 microglial cells : Towards a better understanding of X-linked adrenoleukodystrophy
X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder characterized by very-long-chain fatty acid (VLCFA) accumulation resulting from a peroxisomal β-oxidation defect. The disease is caused by mutations in the ABCD1 gene, which encodes for a peroxisomal half ABC transporter pr...
Polyunsaturated fatty acids role in normal and pathological brain development
The perinatal dietary intake in n-3 and n-6 polyunsaturated fatty acids (PUFAs n-3 and n-6), also known as ‘omega-3’ and ‘omega-6’, is essential for brain development. As these lipids cannot be de novo synthesized by the body, they must be provided by the diet according to a ratio of one n-3 PUFA fo...
Identification of macrophagic and microglial activation programs in progressive forms of multiple sclerosis
Multiple sclerosis (MS) is a chronic neuro-inflammatory disease and the most common cause of chronic neurological disability in young adults. No treatment is currently available to prevent the aggravation of symptoms in the progressive forms of the disease. The involvement of macrophages and microgl...
Role of thyroid hormones in neurological development of cardio-respiratory circuits in rodents
Thyroid hormones are essential for the normal development of the central nervous system. The latter presents a high vulnerability to any thyroid hormones deficiency, especially in the early stages of perinatal development, when the mother is the only source for the foetus. At that time, any maternal...
Neuronal activity drives microglial calcium signaling through purinergic signaling system
Microglial cells are the resident immune cells of the brain. They have mainly been studied under pathological conditions and their functions under physiological conditions are beginning to be understood. In particular, it is now well established that in healthy brain microglia continuously scan the...
Investigating lipid droplets in the developing and adult mouse brain
Most cells in the brain are formed during embryonic development, where neural stern/progenitor cells (NSPCs) divide to generate new NSPCs, neurons and glial cells. NSPCs persist throughout adulthood in some regions and continuously generate new neurons in a process called adult neurogenesis. Lipid m...
Role of plasminogen tissue activator in immune response during autoimmune encephalomyelitis Role of tissue plasminogen activator in immune response during autoimmune encephalomyelitis
Tissue plasminogen activator (tPA) is a serine protease, mainly synthesized by endothelial cells of vessels.Initially discovered in the vascular compartment where its main function is to participate to fibrinolysis, tPA is alsopresent in the cerebral parenchyma, and expressed by several cell types l...
Spontaneous myelin regeneration in the adult mouse brain : crosstalk between stem cells, progenitor cells and microglia
Myelin sheath surrounding axons ensures neuronal support and increases conduction speed. Demyelination can occur in many circumstances leading to neurological deficits. Spontaneous remyelination exists but is highly variable among patients and structures. Parenchymal oligodendrocyte progenitor cells...
Overexpression of APP soluble forms : physiological roles and application to Alzheimer’s disease
One of the main characteristic of Alzheimer’s Disease (AD) is the intracerebral accumulation of the neurotoxic Amyloid β peptide (Aβ) either as oligomeric or aggregated forms known as the amyloid plaques. This peptide is produced via the Amyloid Precursor Protein (APP) processing following the amylo...
Progesterone in Stroke Cerebroprotection : Metabolites, Target Cells, and Role of Neural Progesterone Receptors (PR)
Ischemic stroke initiates a cascade of changes that lead to cell death and also coordinates endogenous processes that counteract the nocuous consequences of ischemia. Understanding these processes is very important for the development of potential neuroprotectants which can be just boosters of endog...
Therapeutic effects of VIP, PACAP, orexins and their analogs in experimental models of multiple sclerosis
Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease of the central nervous system (CNS). First MS symptoms are cognitive deterioration, dizziness, pain, fatigue and loss of vision. In physiological condition, the axons of neurons are surrounded by a myelin sheath synthesize...
Prions diseases : towards the development of gene and cell therapy.
Transmissible spongiform encephalopathies are neurodegenerative diseases characterized by a strong vacuolization, a neuronal lost and deposits of prion pathologic protein: PrPSc. This PrPSc accumulation is the result of the conformational conversion of the host encoded endogenous PrPC protein. Altho...
Genetic Diversity of Innate Immune Response Molecules in Bipolar Disorder
Bipolar disorders (BD) are chronic, multisystem and multifactorial disorders with significant lifetime morbidity, mortality and socioeconomic burden. Understanding its genetic background and triggering environmental factors should improve diagnosis and therapeutic management. Immune dysregulation se...