Janique Guiramand - Academia.edu (original) (raw)

Papers by Janique Guiramand

We have reported that a transient treatment of hippocampal neurons with alpha-tocopherol induced ... more We have reported that a transient treatment of hippocampal neurons with alpha-tocopherol induced a long-lasting protection against oxidative damage mediated by Fe(2+) ions. This protection required protein synthesis. Here, we have studied whether this "hyposensitivity" to oxidative stress could be linked to an altered Ca(2+) homeostasis. Fe(2+) ions triggered a Ca(2+) entry which was required for Fe(2+) ion-induced toxicity. This influx was sensitive to blockers of TRP-like nonspecific Ca(2+) channels, including Ruthenium Red, La(3+), and Gd(3+) ions which also prevented the Fe(2+) ion-induced toxicity and oxidative stress as revealed by protein carbonylation status. The pretreatment with alpha-tocopherol resulted in a reduction of the Ca(2+) increase induced by Fe(2+) ions and masked the blocking effect of La(3+) ions. Moreover, such a pretreatment reduced the capacitive Ca(2+) entries (CCE) observed after metabotropic glutamate receptor stimulation, which are known to in...

British Journal of Pharmacology

Neurochemical research, Jan 20, 2018

Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the ... more Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the offspring. Cognitive/behavioral deficits are supported by changes in synaptic plasticity in different brain areas. We have reported previously that prenatal exposure to bacterial LPS could induce inhibition of hippocampal long-term potentiation (LTP) in the CA1 area of the juvenile/adult male offspring associated with spatial learning inabilities. Nevertheless, deficits in plasticity could be observed at earlier stages as shown by the early loss of long-term depression (LTD) in immature animals. Moreover, aberrant forms of plasticity were also evidenced such as the transient occurrence of LTP instead of LTD in 15-25 day-old animals. This switch from LTD to LTP seemed to involve the activation of metabotropic glutamate receptor subtype 1 and 5 (mGlu1/5). We have thus investigated here whether the long-term depression elicited by the direct activation of these receptors (mGlu-LTD) with a s...

Toxicology Letters, May 1, 1990

Neomycin (an aminoglycoside antibiotic), ethacrynate (a loop diuretic), cisplatin (an anticancer ... more Neomycin (an aminoglycoside antibiotic), ethacrynate (a loop diuretic), cisplatin (an anticancer drug) and mercuric chloride are chemically unrelated drugs which present similar ototoxic and nephrotoxic properties. We have found that all these molecules inhibit inositol phosphate turnover induced by carbachol or glutamate in rat brain synaptoneurosomes. Since this second messenger system appears to be a key mechanism for cell functioning and even survival, our observations raise the possibility that the expression of the specific toxicity of these compounds may result from excessive inhibition of the phosphoinositide cascade.

Current Aspects of the Neurosciences, 1991

International Journal of Developmental Neuroscience, 1989

The evolution of excitatory amino acids-(EAA) stimulated inositol phosphates (IPs) turnover durin... more The evolution of excitatory amino acids-(EAA) stimulated inositol phosphates (IPs) turnover during postnatal development was investigated in synaptoneurosomes prepared from rat forebrains. The two main EAA agonists which induce the IPs synthesis were quisqualate (QA) and N-methyl-D-aspartate (NMDA). The QA and NMDA stimulations of IPs formation present a particular developmental pattern, characterized by an active phase during rat synaptogenesis. The QA-evoked IPs accumulation peaked in synaptoneurosomes prepared from 8-day-old rat forebrains while that evoked by NMDA peaked in synaptoneurosomes from 12-day-old rats. These two developmental patterns are specific of the EAA agonists since the other various neuroactive substances tested (carbachol (Carb), noradrenaline, and high concentrations of potassium) induced an IPs accumulation, which increases during development and reaches a maximum in synaptoneurosomes of adult animals. Aging leads to a decrease in the capability of EAAs and muscarinic agonists to stimulate IPs formation in synaptoneurosomes, whereas the stimulation of IPs turnover by noradrenaline remains constant. Taken together, these results suggest that EAAs play a key role during brain development by sequentially activating two receptor subtypes, a new QA receptor, and a NMDA receptor, linked to the phosphoinositide metabolism. They may also indicate that these EAA-induced IPs responses are related to neuronal plastic events, the amplitude of which decreases with aging.

Hippocampus, 2006

Low frequency-induced short-term synaptic plasticity was investigated in hippocampal slices with ... more Low frequency-induced short-term synaptic plasticity was investigated in hippocampal slices with 60-electrode recording array. Remarkably, the application of low-frequency stimulation (1 Hz) for a short duration (3-5 min) resulted in the induction of a slow-onset longterm potentiation (LTP) in the immediate vicinity of the stimulated electrode. This phenomenon was observed exclusively in the CA1 subfield, neither in the CA3 area nor in the dentate gyrus. The induction of this slow-onset LTP required neither N-methyl-D-aspartate (NMDA) nor non-NMDA ionotropic receptor activation but was strongly dependent on metabotropic glutamate mGlu 5 receptor stimulation and [Ca 2þ ]i increase. In addition, this form of synaptic plasticity was associated with an increase in cAMP concentration and required protein kinase A activation. Paired-pulse facilitation ratio and presynaptic fiber volley amplitude were unaffected when this LTP was triggered, suggesting the involvement of postsynaptic modifications. Although mitogen activated protein kinase pathway was stimulated after the application of low frequency, the induction and maintenance of this slow-onset LTP were not dependent on the activation of this intracellular pathway. The direct activation of adenylyl cyclase with forskolin also induced a synaptic enhancement displaying similar features. This new form of LTP could represent the mnesic engram of mild and repetitive stimulation involved in latent learning. V

Neurochemistry International, 1992

ACS chemical neuroscience, Aug 16, 2017

l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has ... more l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient, and environmentally friendly chemical synthesis of l-theanine and l-γ-N-propyl-Gln and their corresponding d-isomers. l-Theanine, and its derivatives obtained so far, exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons. This activity was retained on NMDA receptors expressed in Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors were equally modulated by l-theanine. The stereochemical change from l-theanine to d-theanine along with the substitution of the ethyl for a propyl moiety in the γ-N position of l- and d-theanine significantly enhanced the biological...

Hippocampus, 2008

Prenatal infection is a major stressful experience leading to enhanced susceptibility for mental ... more Prenatal infection is a major stressful experience leading to enhanced susceptibility for mental illnesses in humans. We recently reported in rats, that oxidative stress and glutathione (GSH) shortage occurred in fetal male brain after lipopolysaccharide (LPS) to the dams and that these responses might be involved in the neurodevelopmental deficits observed in adolescent offspring. Furthermore, pretreatment with N-acetylcysteine (NAC) before LPS avoided both delayed synaptic plasticity and mnesic performance deficits. Since NAC is one of the few medications permitted in pregnant women, this study evaluated the ability of NAC to serve as a protective therapy even after the LPS challenge. Pregnant rats received a single ip injection of E. coli LPS, two days before delivery, and were given NAC in their tap water after the LPS. GSH was evaluated at the time of its expected drop in the hippocampus of male fetuses, whereas long-term potentiation (LTP) in the CA1 area of the hippocampus and spatial memory in the water-maze were recorded in 28-day-old male offspring. Post-treatment with NAC, four hours after the LPS challenge fully prevented the drop in the GSH hippocampal content. LTP, as well as spatial learning were completely protected. NAC administration at delivery also partially restored the LTP whereas post-treatment two days later was inefficient. Another set of dams were supplemented with a-tocopherol prior to LPS exposure, enhancing the a-tocopherol levels in fetal hippocampus. This treatment did not prevent the LPS-induced synaptic plasticity impairment. These results point to fetal hippocampal GSH as a major target of the detrimental effects of in utero LPS challenge. The therapeutic window of NAC extends up to birth, suggesting that this drug might be clinically useful even after an immuno-inflammatory episode. V

Neurochem Res, 1991

The relatively recent discovery that excitatory amino acids (EAAs), besides their known action as... more The relatively recent discovery that excitatory amino acids (EAAs), besides their known action as fast synaptic transmitters via the opening of receptor-associated ion channels, also exert their effects by stimulating the phosphoinositide breakdown (1,2) has required a redefinition of the number and the nature of EAAs receptor subtypes and has opened the way for new roles in brain physiology and pathophysiology (for a review, see 3). In addition to the ionotropic receptor types, namely the N-methyl-D-aspartate (NMDA), the RS,x-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), also called quisqualate/kainate and the kainate (KA) subtypes (4,5), the existence of two metabotropic receptors has been proposed (for a review, see 6). The first one is preferentially activated by quisqualate (QA), not blocked by any of the EAA antagonists of the ionotropic receptors (7,8) and is tentatively named for the moment the quisqualate metabotropic receptor (QAm). The second one preferentially binds ibotenate (IBO), is inhibited by 2-amino-4-phosphonobutyrate (L-AP4) (2,9) and is referred to in this paper as the IBO metabotropic receptor (IBOm). It must be emphasized that the activation of the ionotropic NMDA receptor may also lead to an enhanced phosphoinositide hydrolysis . The transduction machinery, which starts up with the receptor activation to yield the second messengers, inositol phosphates (IPs) and diacylglycerol (DAG), is a multistep mechanism (for reviews, see 10-12). One of these steps is thought to

Cerebral Cortex, Sep 1, 2001

Noradrenergic inputs modulate hippocampal function via distinct receptors. In hippocampal neurona... more Noradrenergic inputs modulate hippocampal function via distinct receptors. In hippocampal neuronal cultures, mRNA expression of adrenoceptor subtypes is maintained from 1 day in vitro (DIV) to 22 DIV. Noradrenaline dose-dependently stimulates phosphoinositide (PI) breakdown in both immature and mature cultures through the activation of α1 receptors. At 22 DIV, basal PI breakdown depends on excitatory synaptic activity since it is decreased by tetrodotoxin or glutamate receptor antagonists. At 22 DIV, a similar decrease of basal PI breakdown is also observed with α1, α2 or β adrenoceptor antagonists. These effects are not additive with that produced by tetrodotoxin. Adrenergic antagonists also strongly reduce spontaneous excitatory post-synaptic currents (sEPSC) as evidenced by whole cell recording. Therefore, in hippocampal cultures, excitatory transmission is modulated by a tonic activation of adrenoceptors probably produced by an endogenous ligand. Indeed, (i) the depletion of catecholamine pools by reserpine also decreases both basal PI metabolism and sEPSC; (ii) hippocampal neurons possess both tyrosine hydroxylase (TH) and dopamine-β-hydroxylase mRNAs, encoding enzymes required for catecholamine synthesis; and (iii) some hippocampal neurons show TH-immunoreactivity. TH-positive cells are also detected in E18 hippocampal sections. Thus, cultured hippocampal neurons synthesize and release an adrenergic-like ligand, which tonically potentiates excitatory synaptic transmission in mature cultures.

Free Radical Biology Medicine, 2007

Molecular Nutrition Food Research, Apr 1, 2010

Pretreatment of cultured hippocampal neurons with a low concentration of alpha-tocopherol (a-TP),... more Pretreatment of cultured hippocampal neurons with a low concentration of alpha-tocopherol (a-TP), the major component of vitamin E, results in a long-lasting protection against oxidative damages, via genomic effects. This neuroprotection is associated with the attenuation of a calcium influx triggered by oxidative agents such as Fe 21 ions. This Ca 21 influx is supported by a TRP-like channel, also partly involved in capacitive calcium entry within neurons. Here, we evidence the contribution of TRPV1 channels in this mechanism. TRPV1 channels are activated by various agents including capsaicin, the pungent component of hot chili peppers and blocked by capsazepine (CPZ) or 5 0 -iodo-resiniferatoxin. Both TRPV1 inhibitors strongly reduced Fe 21 ion-mediated toxicity and Ca 21 influx, in the same way as to a-TP pretreatment. Moreover, CPZ also decreased capacitive calcium entry in hippocampal neurons. Finally, both CPZ and 5 0 -iodo-resiniferatoxin reduced spontaneous excitatory synaptic transmission; this depression of synaptic transmission being largely occluded in a-TP-pretreated neurons. In conclusion, in our experimental model, TRPV1 channels are involved in the Fe 21 ion-induced neuronal death and a negative modulation of this channel activity by a-TP pretreatment may account, at least in part, for the long-lasting neuroprotection against oxidative stress.

Journal of Neurochemistry

In this article, we demonstrate that an increase in intracellular Ca2+ concentration may represen... more In this article, we demonstrate that an increase in intracellular Ca2+ concentration may represent a specific common step(s) in the mechanism@) of action of glutamate (Glu) and depolarizing agents on formation of inositol phosphates (IPS) in 8-day-old rat forebrain synaptoneurosomes. In fact, A23 187, a Caz+ ionophore, induces a dose-dependent accumulation of IPS, which is not additive with that evoked by Glu and K+ but is slightly synergistic with that induced by carbachol. In addition, Glu and K+ augment the intracellular Ca2+ concentration in synaptoneurosome preparations as measured by the fura-2 assay. The absence of external Ca2+ decreases basal and Glu-, and K+-stimulated formation of Ips. Cd2+ (100 p M ) fully inhibits both Glu-and K+-evoked formation of IPS without affecting the carbachol-elicited response of IPS. Zn2+ inhibits Glu-and K+-stimulated accumulation of IPS (IC50 -0.4 mM) but with a lower affinity than Cd2+ (IC50 -0.035 mM). The organic Ca" channel

European Journal of Neuroscience, 2015

Acute effects of ghrelin on excitatory synaptic transmission were evaluated on hippocampal CA1 sy... more Acute effects of ghrelin on excitatory synaptic transmission were evaluated on hippocampal CA1 synapses. Ghrelin triggered an enduring enhancement of synaptic transmission independently of NMDA receptor activation and likely via postsynaptic modifications. This ghrelin-mediated potentiation resulted from the activation of GHS-R1a receptors as it was mimicked by the selective agonist JMV1843 and blocked by the selective antagonist JMV2959. This potentiation also required the activation of PKA and ERK pathways to occur since it was inhibited by KT5720 and U0126, respectively. Moreover it most likely involved Ca2+ influxes as both ghrelin and JMV1843 elicited intracellular Ca2+ increases, which were dependent on the presence of extracellular Ca2+ and mediated by L-type Ca2+ channels opening. In addition, ghrelin potentiated AMPA receptor-mediated [Ca2+]i increases while decreasing NMDA receptor-mediated ones. Thus the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses likely results from postsynaptic mechanisms involving PKA and ERK activation, which are producing long-lasting enhancement of AMPA receptor-mediated responses. This article is protected by copyright. All rights reserved.

Toxicology Letters, 1990

Neomycin [an aminoglycoside antibiotic), ethacrynate (a loop diuretic), cisplatin (an anticancer ... more Neomycin [an aminoglycoside antibiotic), ethacrynate (a loop diuretic), cisplatin (an anticancer drug) and mercuric chloride are chemically unrelated drugs which present similar ototoxic and nephrotoxic properties. We have found that all these molecules inhibit inositol phosphate turnover induced by carbachol or glutamate in rat brain synaptoneurosomes. Since this second messenger system appears to be a key mechanism for cell functioning and even survival, our observations raise the possibility that the expression of the specific toxicity of these compounds may result from excessive inhibition of the phosphoinositide cascade.