Zsolt Lenkei

Zsolt Lenkei
French Institute of Health and Medical Research | Inserm · Institute of Psychiatry and Neurosciences of Paris

MD, PhD

About

100
Publications
13,771
Reads
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4,352
Citations
Additional affiliations
July 2002 - present
École Supérieure de Physique et de Chimie Industrielles
Position
  • Principal Investigator
June 2002 - present
French National Centre for Scientific Research
Position
  • Prinicipal Investigator

Publications

Publications (100)
Article
Full-text available
Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with...
Preprint
Full-text available
Microglia, the main immunocompetent cells of the brain regulate neuronal function in health and disease, but their contribution to cerebral blood flow (CBF) remained elusive. Here we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. We show that microglia establish direct purinergic cont...
Article
Full-text available
There is a critical need for reliable quantitative biomarkers to assess functional brain alterations in mouse models of neuropsychiatric diseases, but current imaging methods measuring drug effects through the neurovascular coupling, face issues including poor sensitivity, drug-induced changes in global brain perfusion and the effects of anesthesia...
Article
Full-text available
Chronic pain pathologies, which are due to maladaptive changes in the peripheral and/or central nervous systems, are debilitating diseases that affect 20% of the European adult population. A better understanding of the mechanisms underlying this pathogenesis would facilitate the identification of novel therapeutic targets. Functional connectivity (...
Article
Full-text available
The default mode network (DMN) has been defined in functional brain imaging studies as a set of highly connected brain areas, which are active during wakeful rest and inactivated during task-based stimulation. DMN function is characteristically impaired in major neuropsychiatric diseases, emphasizing its interest for translational research. However...
Data
Video S2: 3D projection of temporal integration (5 min) of QD localizations around a presynaptic terminal (Figure 3 is related to this video).
Data
Video S1: Time-lapse of hippocampal neurons expressing FLAG-CB1-GFP (green) incubated for 5 minutes with biofunctional QD-pA-anti-FLAG nanoconstructs (magenta) (Figure 1c,d is related to this video).
Article
Full-text available
Single‐particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here, the nano‐resolved population dynamics of QDs is exploited to reconstruct the topography and structural changes of the cell membrane surface wit...
Article
Full-text available
cGMP is critical to a variety of cellular processes, but the available tools to interfere with endogenous cGMP lack cellular and subcellular specificity. We introduce SponGee, a genetically encoded chelator of this cyclic nucleotide that enables in vitro and in vivo manipulations in single cells and in biochemically defined subcellular compartments...
Article
Significance: Our current knowledge of the pathophysiology and molecular mechanisms causing psychiatric disorders is modest, but genetic susceptibility and environmental factors are central to the etiology of these conditions. Autism, schizophrenia, bipolar disorder and major depressive disorder show genetic gene risk overlap and share symptoms and...
Preprint
Full-text available
Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the...
Preprint
Full-text available
Endo- and exocannabinoids, such as the psychoactive component of marijuana, exert their effects on brain function by inducing several forms of synaptic plasticity through the modulation of presynaptic vesicle release. However, the molecular mechanisms underlying the widely expressed endocannabinoid-mediated long-term depression (eCB-LTD), are poorl...
Data
Transcranial functional ultrasound (fUS) imaging in an awake and freely moving mouse using our newly developed ultralight ultrasonic probe and fixation setup.
Chapter
Interaction with the highly regulated local lipid environment is emerging as key dynamic component of cellular function through the control of the structure, conformation, and function of cell-membrane-embedded proteins, such as G-protein-coupled receptors (GPCRs). The type-1 cannabinoid receptor CB1, because of a relatively unstable GPCR structure...
Article
Full-text available
Functional ultrasound (fUS) imaging by ultrasensitive Doppler detection of blood volume was reported to measure adult rat brain activation and functional connectivity with unmatched spatiotemporal sampling (100 µm, 1 ms), but skull-induced attenuation of ultrasonic waves imposed skull surgery or contrast agent use. Also, fUS feasibility remains to...
Article
Full-text available
The DNA- and RNA-binding protein fused in sarcoma (FUS) has been pathologically and genetically linked to amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Cytoplasmic FUS-positive inclusions were identified in the brain and spinal cord of a subset of patients suffering with ALS/FTLD. An increasing number of reports s...
Article
Full-text available
Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination...
Data
Mini dataset presenting in different tabs individual results from Sham and ION treated animals. Each tab shows the results for the following items: ATF3 positive DRG neurons (Fig 1), behaviour (time spent drinking, which provides an indirect measure of mechanical hyperalgesia, Fig 2), intrinsic optical imaging (Fig 3), c-fos expression in the S1BF...
Data
Table reporting the number of animals included in the initial experimental design, and the reasons for the exclusion of some of them during the course of the study. For instance, some animals were excluded from the imaging experiments when they lost some of their whiskers, or from the behavioural analysis if they were not drinking during the habitu...
Article
Full-text available
Blebbistatin is a commonly used molecular tool for the specific inhibition of various myosin II isoforms both in vitro and in vivo. Despite its popularity, the use of blebbistatin is hindered by its poor water-solubility (below 10 micromolar in aqueous buffer) and blue-light sensitivity, resulting in the photoconversion of the molecule, causing sev...
Article
Full-text available
In many species, adolescence is a critical phase in which the endocannabinoid system can regulate the maturation of important neuronal networks that underlie cognitive function. Therefore, adolescents may be more susceptible to the neural consequences of chronic cannabis abuse. We reported previously that chronically exposing adolescent rats to the...
Article
Full-text available
Non-invasive imaging deep into organs at microscopic scales remains an open quest in biomedical imaging. Although optical microscopy is still limited to surface imaging owing to optical wave diffusion and fast decorrelation in tissue, revolutionary approaches such as fluorescence photo-activated localization microscopy led to a striking increase in...
Article
Full-text available
Distinctive optical properties of inorganic quantum dot (QD) nanoparticles promise highly-valuable probes for fluorescence-based detection methods, particularly for in-vivo diagnostics, cell phenotyping via multiple markers or single molecule tracking. However, despite high hopes, this promise has not been fully realized yet, mainly due to difficul...
Article
Full-text available
Long-term inspection of biological phenomena requires probes of elevated intra- and extracellular stability and target biospecificity. The high fluorescence and photostability of quantum dot (QD) nanoparticles contributed to foster their promise as bioimaging tools that could overcome limitations associated with traditional fluorophores. However, Q...
Article
Full-text available
We have recently reported cannabinoid-induced rapid changes in the structure of individual neurons. In order to investigate the presence of similar effects at the regional level, measures of brain tissue biomechanics are required. However, cannabinoids are known to alter cerebral blood flow (CBF), putatively resulting in presently unexplored change...
Article
Full-text available
Functional ultrasound (fUS) is a novel neuroimaging technique, based on high-sensitivity ultrafast Doppler imaging of cerebral blood volume, capable of measuring brain activation and connectivity in rodents with high spatiotemporal resolution (100 μm, 1 ms). However, the skull attenuates acoustic waves, so fUS in rats currently requires craniotomy...
Article
We propose a structured illumination microscopy method to combine super resolution and optical sectioning in three-dimensional (3D) samples that allows the use of two-dimensional (2D) data processing. Indeed, obtaining super-resolution images of thick samples is a difficult task if low spatial frequencies are present in the in-focus section of the...
Article
Full-text available
Painful experiences are multilayered, composed of sensory, affective, cognitive and behavioral facets. Whereas it is well accepted that the development of chronic pain is due to maladaptive neuronal changes, the underlying molecular mechanisms, their relationship to the different pain modalities, and indeed the localization of these changes are sti...
Article
Full-text available
Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast functional ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep in the anaesthetized rodent brain, through a large thinned-skull cranial window,...
Article
Full-text available
Endocannabinoids are recently recognized regulators of brain development, but molecular effectors downstream of type-1 cannabinoid receptor (CB1R)-activation remain incompletely understood. We report atypical coupling of neuronal CB1Rs, after activation by endo- or exocannabinoids such as the marijuana component ∆9-tetrahydrocannabinol, to heterotr...
Article
Full-text available
Neurons display important differences in plasma membrane composition between somatodendritic and axonal compartments, potentially leading to currently unexplored consequences in G-protein-coupled-receptor signaling. Here, by using highly-resolved biosensor imaging to measure local changes in basal levels of key signaling components, we explored fea...
Conference Paper
Full-text available
Introduction: Recent studies suggest a significant influence of type-1 cannabinoïd receptors (CB 1 R) on the puberty maturation processes [1] including neuronal remodeling and modifications of cortical mechanical properties in the postnatal brain. A preliminary study showed a decrease of the hippocampus elasticity within 15 minutes after CB 1 R ago...
Article
Full-text available
Directionality of information flow through neuronal networks is sustained, at the cellular level, by polarized neurons. However, specific targeting or anchoring motifs, responsible for polarized distribution on the neuronal surface, have only been identified for a few neuronal G-protein-coupled receptors (GPCRs). Here, through mutational and pharma...
Conference Paper
Full-text available
Background: Recent studies suggest a significant influence of type-1 cannabinoïd receptors (CB1R) on the puberty maturation processes [1] including neuronal remodeling and modifications of cortical mechanical properties in the postnatal brain. A preliminary study showed a decrease of the hippocampus elasticity within 15 minutes after CB1R agonist i...
Conference Paper
Full-text available
October 5 ESMRMB 2012 195 Figure 4: CBF and dispersion maps obtained from NSRopt in a subject with a stenosis in the right carotid. Figures 1 and 2 present the impressive improvement in the optimized NSR (NSR opt) compared to the original version (NSR orig) in terms of both com-putational time and presence of outlier voxels. NSR opt provides physio...
Article
Full-text available
Chronic cannabinoid exposure results in tolerance due to region-specific desensitization and down-regulation of CB1 cannabinoid receptors (CB1Rs). For most G-protein-coupled receptors, internalization closely follows rapid desensitization as an important component of long-term down-regulation. However, in vivo patterns of CB1R internalization are n...
Article
Full-text available
The type-1 cannabinoid receptor (CB1R) was initially identified as the neuronal target of Δ(9)-tetrahydrocannabinol (THC), the major psychoactive substance of marijuana. This receptor is one of the most abundant G-protein-coupled receptors in the adult brain, the target of endocannabinoid ligands and a well-characterized retrograde synaptic regulat...
Conference Paper
Full-text available
Introduction: Recent studies suggest a significant influence of type-1 cannabinoïd receptors (CB 1 R) on puberty maturation processes [1]. It could result in neuronal remodeling in the postnatal brain and also lead to local modifications of cortical mechanical properties. The objective of this study was to use MR Elastography to identify local temp...
Article
By analogy to other axonal proteins, transcytotic delivery following spontaneous endocytosis from the somatodendritic membrane is expected to be essential for polarized distribution of axonal G-protein coupled receptors (GPCRs). However, possible contribution from constitutive activation, which may also result in constitutive GPCR endocytosis, is p...
Article
Several lines of evidence support a strong relationship between cholesterol and Alzheimer's disease pathogenesis. Membrane cholesterol is known to modulate amyloid precursor protein (APP) endocytosis and amyloid-beta (Abeta) secretion. Here we show in a human cell line model of endocytosis (HEK293 cells) that cholesterol exerts these effects in a d...
Article
We have developed a novel surface coating for semiconductor quantum dots (QDs) based on a heterobifunctional ligand that overcomes most of the previous limits of these fluorescent probes in bioimaging applications. Here we show that QDs capped with bidentate zwitterionic dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands are a favorable alternative...
Article
Several lines of evidence support a strong relationship between cholesterol and Alzheimer's disease pathogenesis. Membrane cholesterol is known to modulate amyloid precursor protein (APP) endocytosis and amyloid-β (Aβ) secretion. Here we show in a human cell line model of endocytosis (HEK293 cells) that cholesterol exerts these effects in a dose-de...