Monique Esclapez | Aix-Marseille University (original) (raw)

Papers by Monique Esclapez

In 1888, Ramon y Cajal suggested that the contacts between the axon terminals of a neuron and the... more In 1888, Ramon y Cajal suggested that the contacts between the axon terminals of a neuron and the dendrites or the perikaryon of another neuron are the points at which information flows from one neuron to the other. The term synapse was introduced by Sherrington (1897) to describe these zones of contact between neurons, specialized in the transmission of information. In fact, the term ‘synapse’ is not used exclusively to describe connections between neurons (interneuronal connections) but also those between neurons and effector cells such as muscular and glandular cells (neuroeffector synapses) and those between receptive cells and neurons. These contacts are the points where the information is transmitted from one cell to the other: synaptic transmission. According to morphological and functional criteria, there are various types of synapses, including chemical, electrical and mixed types.

Frontiers in Cellular Neuroscience, Oct 1, 2019

Psychoactive drugs used during pregnancy can affect the development of the brain of offspring, di... more Psychoactive drugs used during pregnancy can affect the development of the brain of offspring, directly triggering neurological disorders or increasing the risk for their occurrence. Caffeine is the most widely consumed psychoactive drug, including during pregnancy. In Wild type mice, early life exposure to caffeine renders offspring more susceptible to seizures. Here, we tested the long-term consequences of early life exposure to caffeine in THY-Tau22 transgenic mice, a model of Alzheimer's disease-like Tau pathology. Caffeine exposed mutant offspring developed cognitive earlier than water treated mutants. Electrophysiological recordings of hippocampal CA1 pyramidal cells in vitro revealed that early life exposure to caffeine changed the way the glutamatergic and GABAergic drives were modified by the Tau pathology. We conclude that earlylife exposure to caffeine affects the Tau phenotype and we suggest that caffeine exposure during pregnancy may constitute a risk-factor for early onset of Alzheimer's disease-like pathology.

The Journal of Neuroscience, Oct 1, 1993

HAL (Le Centre pour la Communication Scientifique Directe), Nov 11, 2017

HAL (Le Centre pour la Communication Scientifique Directe), May 17, 2017

in the rat pilocarpine model of temporal lobe epilepsy: evidence for axon terminal sprouting

Science, 2021

Synapse stabilization Early in brain development, neurons connect to each other enthusiastically.... more Synapse stabilization Early in brain development, neurons connect to each other enthusiastically. With development, an overabundance of synapses is winnowed down to refine efficiently connected circuits. Inactive synapses are prime targets for elimination, whereas active synapses tend to be retained. Gomez-Castro et al . took a closer look at how those choices are made (see the Perspective by Blum and Lopes). When postsynaptic adenosine receptors are muted or do not find enough extracellular adenosine, synapses get eliminated. Neurotransmitter-dependent signaling pathways drive protein kinase A to phosphorylate the postsynaptic scaffolding molecule gephyrin. Together with a partner synaptogenic membrane protein, gephyrin is required for the stabilization of γ-aminobutyric acid receptors. Adenosine receptors thus detect synaptic activity and in turn drive the stabilization of synapses that produce such activity. —PJH

Journal of Neurophysiology, 1996

1. Graded N-methyl-D-aspartate receptor (NMDAR)-dependent epileptiform discharges were recorded f... more 1. Graded N-methyl-D-aspartate receptor (NMDAR)-dependent epileptiform discharges were recorded from ex vivo hippocampal slices obtained from rats injected a week earlier with an intracerebroventricular dose of kainic acid. Intracellular recordings from pyramidal cells of the CA1 area showed that glutamate NMDAR actively participated in synaptic transmission, even at resting membrane potential. When NMDAR were pharmacologically isolated, graded burst discharges could still be evoked. 2. The oxidizing reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB, 200 microM, 15 min) suppressed the late part of the epileptiform burst that did not recover after wash but could be reinstated by the reducing agent tris (2-carboxyethyl) phosphine (TCEP, 200 microM, 15 min) and again abolished with the NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 3. Pharmacologically isolated NMDAR-mediated responses were decreased by DTNB (56 +/- 10%, mean +/- SD, n = 6), an effect reversed by TCEP. ...

Gamma-Aminobutyric acidergic (GABAergic) neurons that correspond mainly to local circuit neurons ... more Gamma-Aminobutyric acidergic (GABAergic) neurons that correspond mainly to local circuit neurons play a crucial role in regulating the activity of cortical neuronal networks and the complex interactions among principal neurons. These functions depend on a very heterogeneous population of neurons, whose number and diversity may increase during mammalian evolution. Interestingly dysfunction and cell death of several specific types of GABAergic neurons is a hallmark of various psychiatric and neurological disorders such as schizophrenia, autism and epilepsies to which defect in genesis or migration of these neurons can be a predisposing factor. Understanding primate specific developmental mechanisms that regulate generation, migration and maturation of cortical GABA neurons, is a crucial step in elucidating such pathologies. However, there are few such studies in monkeys and humans, whereas they are numerous in lower mammals. In rodents, cortical GABAergic neurons are generated exclusively in the subcortical proliferative zone of the ventral telencephalon, the ganglionic eminence (GE), and migrate tangentially to the dorsal telencephalon to reach their target cortical layer. We reported (Petanjek et al. 2009, Cerebral Cortex 19:249-62) that in contrast to rodents, in cynomolgus monkey cortical GABAergic neurons are generated massively in the proliferative zones of the dorsal telencephalon, in addition to the GE. This neurogenesis occurs very early during brain development in both dorsal and ventral telencephalon but with distinct temporal profiles. GABAergic neuron progenitors labeled for transcription factor Mash1 and GABA synthesizing enzyme GAD65 were present mainly in the GE at embryonic days (E) 47-55, and in the entire dorsal telencephalon at E64-75. These progenitors within the dorsal telencephalon are generated locally rather than in the GE. In the human embryonic forebrain (Letinic et al. 2002, Nature 417:645-9) retroviral labeling in organotypic slice cultures also demonstrated the existence of two distinct lineages of neocortical GABAergic neurons. One lineage expresses Dlx1/2 and Mash1 transcription factors, represents 65% of neocortical GABAergic neurons in humans, and originates from Mash1-expressing progenitors of the neocortical proliferative zones of the dorsal telencephalon. The second lineage, characterized by the expression of Dlx1/2 but not Mash1, forms in human brain only around 35% of the GABAergic neurons and originates from the GE of the ventral forebrain, in comparison to rodent where all GABAergic neurons originate in GE. The dorsal telencephalic origin of cortical GABA-ergic neurons is a unique feature of human and non-human primates and appears to be, in the primate lineage, an early evolutionary modification which provided increased number and variety of GABA-ergic neurons to an expanding neocortex.

Http Www Theses Fr, 2009

L’association entre activation de p25/Cdk5 et un nombre varie de maladies neurodegeneratives, l’e... more L’association entre activation de p25/Cdk5 et un nombre varie de maladies neurodegeneratives, l’effet neuroprotecteur de l’inhibition de la calpaine et/ou de l’activite de cdk5 ainsi que la recapitulation des elements cles du phenotype de type maladie d’Alzheimer chez les souris surexprimant p25 sont des arguments tres forts en faveur du role critique et crucial de p25/cdk5 comme inducteur de la mort neuronale dans ces maladies touchant le systeme nerveux central et particulierement celle d’Alzheimer. Ce processus est provoque par l’hyperphosphorylation de tau, la perte d'integrite du cytosquelette ainsi que celle de la mitochondrie, couplee a la production de radicaux libres et a la reentree dans le cycle cellulaire. Dans cette etude nous avons utilise le modele de souris Ck-p25 pour etudier l’implication de p53 dans ces evenements et pour savoir si p53 est un element primordial en aval de p25/cdk5 pour induire le stress cellulaire et la mort neuronale. Les resultats obtenus montrent que, suite a la surexpression de p25, l’inhibition de p53 a la fois genetique et pharmacologique est capable de bloquer la reentree dans le cycle cellulaire, la creation de radicaux libres et la mort cellulaire, avec un effet benefique sur le comportement et les capacites de memorisation de ces souris dans le test du « fear conditioning ». Pour nous permettre de publier ce travail et pour mieux comprendre le mecanisme de l’induction de la mort neuronale par p25, nous chercherons a savoir quel est l’effet de l’activation de p53 par p25 sur HDAC1. En jouant sur l’inhibition pharmacologique de p53 ou sa surexpression par transfection nous chercherons :1- quel est le mecanisme d’action de p53 sur le niveau d’expression et l’activite de HDAC1, 2- si cet effet est implique dans le role de p53 comme activateur des dommages a l’ADN et de la mort neuronale suite a l’activation de p25. L’utilisation d’une forme mitochondriale de p53 devrait egalement nous dire si la fonction mitochondriale de p53 est importante pour induire ces effets deleteres. Dans cette etude nous avons utilise le modele de souris Ck-p25 pour etudier l’implication de p53 dans ces evenements et pour savoir si p53 est un element primordial en aval de p25/cdk5 pour induire le stress cellulaire et la mort neuronale. Les resultats obtenus montrent que, suite a la surexpression de p25, l’inhibition de p53 a la fois genetique et pharmacologique est capable de bloquer la reentree dans le cycle cellulaire, la creation de radicaux libres et la mort cellulaire, avec un effet benefique sur le comportement et les capacites de memorisation de ces souris dans le test du « fear conditioning ». Pour nous permettre de publier ce travail et pour mieux comprendre le mecanisme de l’induction de la mort neuronale par p25, nous chercherons a savoir quel est l’effet de l’activation de p53 par p25 sur HDAC1. En jouant sur l’inhibition pharmacologique de p53 ou sa surexpression par transfection nous chercherons :1- quel est le mecanisme d’action de p53 sur le niveau d’expression et l’activite de HDAC1, 2- si cet effet est implique dans le role de p53 comme activateur des dommages a l’ADN et de la mort neuronale suite a l’activation de p25. L’utilisation d’une forme mitochondriale de p53 devrait egalement nous dire si la fonction mitochondriale de p53 est importante pour induire ces effets deleteres. Dans cette etude nous avons utilise le modele de souris Ck-p25 pour etudier l’implication de p53 dans ces evenements et pour savoir si p53 est un element primordial en aval de p25/cdk5 pour induire le stress cellulaire et la mort neuronale. Les resultats obtenus montrent que, suite a la surexpression de p25, l’inhibition de p53 a la fois genetique et pharmacologique est capable de bloquer la reentree dans le cycle cellulaire, la creation de radicaux libres et la mort cellulaire, avec un effet benefique sur le comportement et les capacites de memorisation de ces souris dans le test du « fear conditioning ». Pour nous permettre de publier ce travail et pour mieux comprendre le mecanisme de l’induction de la mort neuronale par p25, nous chercherons a savoir quel est l’effet de l’activation de p53 par p25 sur HDAC1. En jouant sur l’inhibition pharmacologique de p53 ou sa surexpression par transfection nous chercherons :1- quel est le mecanisme d’action de p53 sur le niveau d’expression et l’activite de HDAC1, 2- si cet effet est implique dans le role de p53 comme activateur des dommages a l’ADN et de la mort neuronale suite a l’activation de p25. L’utilisation d’une forme mitochondriale de p53 devrait egalement nous dire si la fonction mitochondriale de p53 est importante pour induire ces effets deleteres. Dans cette etude nous avons utilise le modele de souris Ck-p25 pour etudier l’implication de p53 dans ces evenements et pour savoir si p53 est un element primordial en aval de p25/cdk5 pour induire le stress cellulaire et la mort neuronale. Les resultats obtenus montrent que, suite a la…

Sleep Medicine, 2017

Introduction: When hypersomnolence is suspected, children and their parents are routinely screene... more Introduction: When hypersomnolence is suspected, children and their parents are routinely screened using one of a number of available surveys. The vocabulary used in these surveys is sleep-specific and possibly adultoriented, thus it is questionable whether younger children really do comprehend the intent of the questions. The present study aimed to identify children's understanding of the terminology utilised in sleep surveys, particularly the Paediatric Daytime Sleepiness Scale (PDSS). The PDSS was originally developed by Drake, Nickel, Burduvali, Roth, Jefferson, and Badia (2003) as a measure of sleepiness for 11-15 year olds. Nixon, Wawruszak, Verginis, and Davey (2006) then evaluated the use of the PDSS in elementary school children (5-12.9 years). Neither study commented on the sleep vocabulary used within the scale nor whether additional explanations of each question were given to the children by adults administering the scale. Materials and methods: This school-based community study surveyed all students from a regional primary school, aged 4 through to 12 years, their parents/guardians, and their teachers using the Paediatric Daytime Sleepiness Scale (PDSS) and a background information survey completed by a carer. 52 percent of the 727 student and carer surveys distributed were returned; and 67 percent of the teachers responded. Prior to commencing the PDSS, each child was asked the meaning of seven key words used in the questions: drowsy, sleepy, alert, awakened, tired, fatigued, and awake. Their responses were recorded/scribed by their carer on the front page of the child's questionnaire. This study utilised these qualitative data, i.e. the actual definition of each word tendered by each child. Results: The final vocabulary sample consisted of word definitions from 325 children. The qualitative data yielded perceptions reflective of the developmental expressive vocabulary ability of each child: younger children gave more literal and concrete definitions, often with an example from their own life, whilst older children were more global in their choice of vocabulary to define each word. Interestingly, the oldest groups (10, 11 and 12 year olds) frequently chose more abstract words when generating their definitions. The word fatigued, for example, was the most challenging for children to define, with only 2% of 4-5 year olds (N ¼ 51) through to only 30% of 11-12 year olds (N ¼ 40) able to give an approximate definition through inclusion of words such as exhausted, weary, or very tired in their definition. Of the other six words included in this survey, drowsy, alert, and awakened were similarly challenging for the children to define. Conclusions: Sleepiness surveys are frequently utilised by professionals in various capacities, including in research and prior to clinical sleep studies, to gain insight into a child's own perception of their hypersomnolence. However, the vocabulary in these surveys is sleep-specific, and in the case of the PDSS as investigated through this study, utilises vocabulary not in general use by children. Giving a brief definition of these key words prior to administering the survey may yield a more accurate reflection of a child's sleep and daytime behaviours.

Telencephalic GABA-ergic interneurons are very heterogeneous population that differs by their mor... more Telencephalic GABA-ergic interneurons are very heterogeneous population that differs by their morphology, neurochemical contents, specificity of their connections and their physiological properties. In rodent all hippocampal and almost all cortical GABA-ergic interneurons are generated in the ventral (basal, subcortical) proliferative zones, the ganglionic eminence, and migrate tangentially to their target regions. Evolution of the cortex increased extremely the distance that interneurons have to pass, so in human fetuses migration of interneurons becomes extremely complex and more vulnerable event then in any other species. This might explain why disturbances of the GABA-ergic network are found in majority of neurological and psychiatric disorders. To study migrational routes of prospective GABA-ergic interneurons we describe spatial and temporal patterns of tangentionaly and nonradialy migrating like cells on frontal sectioned slices of the human fetal brain in period from 13.5 to...

Somatostatin cells are frequently described as a major population of GABAergic neurons in the cer... more Somatostatin cells are frequently described as a major population of GABAergic neurons in the cerebral cortex, however, a comprehensive analysis of their molecular expression, morphological features and laminar distribution has not yet been performed. In this study, we provided a detailed description of somatostatin neurons in the human prefrontal cortex, including their proportion in the total neuron population, laminar distribution, neurotransmitter phenotype as well as their molecular and morphological characteristics using immunofluorescence and RNAscope in situ hybridization. We found that somatostatin neurons comprise around 7% of neocortical neurons in the human Brodmann areas 9 and 14r, without significant difference between the two regions. Somatostatin cells were NeuN positive and synthesized vesicular GABA transporter and glutamate decarboxylase 1 and 2, confirming their neuronal nature and GABAergic phenotype. Somatostatin cells in the upper cortical layers were small, h...

In human most cortical g-aminobutyric acidergic (GABAergic) neurons are produced in the prolifera... more In human most cortical g-aminobutyric acidergic (GABAergic) neurons are produced in the proliferative zones of the dorsal telencephalon in contrast to rodents. We report that in cynomolgus monkey fetuses cortical GABAergic neurons are generated in the proliferative zones of the dorsal telencephalon, in addition to the proliferative region of the ventral telencephalon, the ganglionic eminence (GE), however, with a temporal delay. GABAergic neuron progenitors labeled for Mash1 and GAD65 were present mainly in the GE at embryonic days (E) 47--55, and in the entire dorsal telencephalon at E64--75. These progenitors within the dorsal telencephalon are generated locally rather than in the GE. The ventral and dorsal lineages of cortical GABAergic neurons display different laminar distribution. Early generated GABAergic neurons from the GE mostly populate the marginal zone and subplate, whereas cortical plate GABAergic neurons originate from both ventral and dorsal telencephalon. A differen...