Author
Françoise Mennicken
Other affiliations: French Institute of Health and Medical Research, McGill University, La Salle University
Bio: Françoise Mennicken is an academic researcher from AstraZeneca. The author has contributed to research in topics: Striatum & Dopaminergic. The author has an hindex of 22, co-authored 26 publications receiving 2032 citations. Previous affiliations of Françoise Mennicken include French Institute of Health and Medical Research & McGill University.
Topics: Striatum, Dopaminergic, Acetylcholine, Neuropeptide, Receptor
Papers
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TL;DR: It is shown that the segregated DOR and MOR distribution is paralleled by a remarkably selective functional contribution of the two receptors to the control of mechanical and heat pain, respectively.
429 citations
TL;DR: Current data suggest Chemokines involvement in the maintenance of CNS homeostasis, in neuronal patterning during ontogeny and as potential mediators of neuroinflammation, playing an essential role in leukocyte infiltration into the brain.
273 citations
TL;DR: The findings indicate that GALR3 mRNA expression in the rat brain is discrete and highly restricted, concentrated mainly in the preoptic/hypothalamic area and the neuroanatomical distribution of GalR3 suggests it might be involved in mediating documented effects of galanin on food intake, fluid homeostasis, cardiovascular function and nociception.
198 citations
TL;DR: It is demonstrated that DRG neurons express perikaryal δORs accessible to CSF-circulating ligands and that the density and, hence, presumably also the responsiveness, of these receptors may be modulated by both pain-related stimuli and sustained exposure to μOR agonists.
Abstract: The present study demonstrates that perikaryalδ-opioid receptors (δORs) in rat dorsal root ganglion (DRG) neurons bind and internalize opioid ligands circulating in the CSF. Using confocal and electron microscopy, we found that prolonged morphine treatment increased the cell surface density of these perikaryal δORs and, by way of consequence, receptor-mediated internalization of the fluorescent deltorphin (DLT) analog ω-Bodipy 576/589 deltorphin-I 5-aminopentylamide (Fluo-DLT) in all three types of DRG neurons (small, medium, and large). In contrast, chronic inflammatory pain induced by the injection of complete Freund's adjuvant (CFA) into one hindpaw selectively increased Fluo-DLT internalization in small and medium-sized DRG neurons ipsilateral to the inflammation. Based on our previous studies in the spinal cord of μ-opioid receptor (μOR) knock-out mice, it may be assumed that the enhanced membrane recruitment of δORs observed after sustained morphine is attributable to stimulation of μORs. However, the selectivity of the effect induced by inflammatory pain suggests that it involves a different mechanism, namely a modality-specific and pain-related activation of C and Aδ fibers. Indeed, stimulation by capsaicin of transient receptor potential vanilloid 1 receptors, which are selectively expressed by small diameter (< 600 μm2) DRG neurons, increased Fluo-DLT internalization exclusively in this cell population. The present results, therefore, demonstrate that DRG neurons express perikaryal δORs accessible to CSF-circulating ligands and that the density and, hence, presumably also the responsiveness, of these receptors may be modulated by both pain-related stimuli and sustained exposure to μOR agonists.
155 citations
TL;DR: It is demonstrated that DOR activation at the central terminals of myelinated mechanoreceptors depresses synaptic input to the spinal dorsal horn, via the inhibition of voltage-gated calcium channels, which reveals a molecular mechanism by which opioids modulate cutaneous mechanosensation.
130 citations
Cited by
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TL;DR: Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
3,394 citations
TL;DR: The concept that the hippocampus and the midbrain dopaminergic neurons of the ventral tegmental area (VTA) form a functional loop is developed and support a model whereby the hippocampal-VTA loop regulates the entry of information into long-term memory.
1,728 citations
TL;DR: Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context.
Abstract: Cytokines constitute a significant portion of the immuno- and neuromodulatory messengers that can be released by activated microglia. By virtue of potent effects on resident and invading cells, microglial cyto- and chemokines regulate innate defense mechanisms, help the initiation and influence the type of immune responses, participate in the recruitment of leukocytes to the CNS, and support attempts of tissue repair and recovery. Microglia can also receive cyto- and chemokine signals as part of auto- and paracrine communications with astrocytes, neurons, the endothelium, and leukocyte infiltrates. Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context. In principle, microglial activation aims at CNS protection. However, failed microglial engagement due to excessive or sustained activation could significantly contribute to acute and chronic neuropathologies. Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions as they are sensitive to cytokine signaling.
1,508 citations
TL;DR: Although there is still little evidence that inflammation triggers or promotes Alzheimer disease, increasing evidence from mouse models suggests that certain inflammatory mediators are potent drivers of the disease.
Abstract: Alzheimer disease is a progressive dementia with unknown etiology that affects a growing number of the aging population. Increased expression of inflammatory mediators in postmortem brains of people with Alzheimer disease has been reported, and epidemiological studies link the use of anti-inflammatory drugs with reduced risk for the disorder. On the initial basis of this kind of evidence, inflammation has been proposed as a possible cause or driving force of Alzheimer disease. If true, this could have important implications for the development of new treatments. Alternatively, inflammation could simply be a byproduct of the disease process and may not substantially alter its course. Or components of the inflammatory response might even be beneficial and slow the disease. To address these possibilities, we need to determine whether inflammation in Alzheimer disease is an early event, whether it is genetically linked with the disease and whether manipulation of inflammatory pathways changes the course of the pathology. Although there is still little evidence that inflammation triggers or promotes Alzheimer disease, increasing evidence from mouse models suggests that certain inflammatory mediators are potent drivers of the disease. Related factors, on the other hand, elicit beneficial responses and can reduce disease.
1,173 citations
TL;DR: Since many inflammatory responses are beneficial, directing and instructing the inflammatory machinery may be a better therapeutic objective than suppressing it.
1,128 citations