MS imaging and absorption methods visualizing sun filter skin spatial distribution and penetration.

Sunscreens must now be effective in protecting skin from ultraviolet, as well as visible/infrared radiation. Here, TriAsorB, a new broad-spectrum sun filter, was formulated with three other sunscreens and their distribution on human skin was studied using a standard penetration protocol and two novel mass spectrometry imaging techniques: atmospheric pressure matrix assisted laser desorption ionization (AP-MALDI) coupled to high resolution mass spectrometry and time of flight - secondary ion mass spectrometry (ToF-SIMS). The standard penetration protocol showed that sun filters absorption was very low, with most of the dose recovered at the surface (none entered the receptor fluid).

Penetration study of formulated nanosized titanium dioxide in models of damaged and sun-irradiated skins.

Inorganic ultraviolet filters such as titanium dioxide (TiO(2)), safe to use on healthy skin, are often applied on compromised and irradiated skin. The aim of this study was to evaluate in vitro the cutaneous penetration of TiO(2) nanoparticles (≥20 nm primary size), included in a sunscreen, in intact, damaged, irradiated, and damaged/irradiated pigskin. Cutaneous penetration and localization of TiO(2) after a 24-h sunscreen application were investigated quantitatively using inductively coupled plasma-mass spectrometry, and qualitatively using transmission electron microscopy (TEM).

Role of the vesicular transporter VGLUT3 in retrograde release of glutamate by cerebellar Purkinje cells.

In the cerebellum, retrograde release of glutamate (Glu) by Purkinje cells (PCs) participates in the control of presynaptic neurotransmitter release responsible for the late component of depolarization-induced suppression of excitation (DSE), as well as for depolarization-induced potentiation of inhibition (DPI). It might also participate in the depolarization-induced slow current (DISC) in PCs, although this contribution was later challenged. We also know that both DPI and DISC are soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent processes, although the molecular nature of the vesicular transporter was not determined.

Role of presynaptic kainate receptors at parallel fiber-purkinje cell synapses in induction of cerebellar LTD: interplay with climbing fiber input.

Until recently, except for A1 adenosine, N-methyl-d-aspartate, and cannabinoid receptors, little effort has been made to unravel possible roles of parallel fiber (PF) presynaptic receptors in long-term depression (LTD) of synaptic transmission at PF-Purkinje cell (PC) synapses. Presynaptic kainate (KA) receptors are also present on PFs and might also influence LTD induction by modulating glutamate (Glu) release at PF-PC synapses. This hypothesis was tested by comparing the efficacy of two pairing protocols in inducing LTD in adult wild-type and knock-out mice for the Glu receptor 6 (GluR6) subunit of KA receptors.

Developmental changes in agonist-induced retrograde signaling at parallel fiber-Purkinje cell synapses: role of calcium-induced calcium release.

In cerebellar Purkinje cells (PCs), activation of postsynaptic mGluR1 receptors inhibits parallel fiber (PF) to PC synaptic transmission by retrograde signaling. However, results were conflicting with respect to whether endocannabinoids or glutamate (Glu) is the retrograde messenger involved. Experiments in cerebellar slices from 10- to 12-day-old rats and mice confirmed that suppression of PF-excitatory postsynaptic currents (EPSCs) by mGluR1 agonists was entirely blocked by cannabinoid receptor antagonists at this early developmental stage.

Developmental changes in retrograde messengers involved in depolarization-induced suppression of excitation at parallel fiber-Purkinje cell synapses in rodents.

At parallel fiber (PF) to Purkinje cell (PC) synapses, depolarization-induced suppression of excitation (DSE) and suppression of PF-excitatory postsynaptic currents (EPSCs) by activation of postsynaptic mGluR1 glutamate (Glu) receptors involve retrograde release of endocannabinoids. However, Levenes et al. suggested instead that Glu was the retrograde messenger in this latter case.

Mechanisms underlying cannabinoid inhibition of presynaptic Ca2+ influx at parallel fibre synapses of the rat cerebellum.

Activation of CB1 cannabinoid receptors in the cerebellum acutely depresses excitatory synaptic transmission at parallel fibre-Purkinje cell synapses by decreasing the probability of glutamate release. This depression involves the activation of presynaptic 4-aminopyridine-sensitive K(+) channels by CB1 receptors, which in turn inhibits presynaptic Ca(2+) influx controlling glutamate release at these synapses. Using rat cerebellar frontal slices and fluorometric measures of presynaptic Ca(2+) influx evoked by stimulation of parallel fibres with the fluorescent dye fluo-4FF, we tested whether the CB1 receptor-mediated inhibition of this influx also involves a direct inhibition of presynaptic voltage-gated calcium channels.

Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy.

Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons.

In rat prefrontal cortex (the prelimbic area of medial frontal cortex), the induction of long-term depression (LTD) and long-term potentiation (LTP) of glutamatergic synapses is powerfully modulated by dopamine. The presence of dopamine in the bathing medium facilitates LTD in slice preparations, whereas in the anesthetized intact brain, dopamine released from dopaminergic axon terminals in the prefrontal cortex facilitates LTP. Dopaminergic facilitation of LTD is at least partly achieved by postsynaptic biochemical mechanisms in which enzymatic processes triggered by dopamine receptor activation cooperate with those triggered by glutamate metabotropic receptor activation.

Direct and indirect interactions between cannabinoid CB1 receptor and group II metabotropic glutamate receptor signalling in layer V pyramidal neurons from the rat prefrontal cortex.

At proximal synapses from layer V pyramidal neurons from the rat prefrontal cortex, activation of group II metabotropic glutamate receptors (group II mGlu) by (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine (DCG IV) induced a long-lasting depression of excitatory postsynaptic currents. Paired-pulse experiments suggested that the depression was expressed presynaptically. Activation of type 1 cannabinoid receptors (CB1) by WIN 55,212-2 occluded the DCG IV-induced depression in a mutually occlusive manner.

Long-term depression induced by postsynaptic group II metabotropic glutamate receptors linked to phospholipase C and intracellular calcium rises in rat prefrontal cortex.

We have previously shown (Otani et al., 1999b) that bath application of (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV), the agonist of group II metabotropic glutamate receptors (mGluRs), induces postsynaptic Ca2+-dependent long-term depression (LTD) of layer I-II to layer V pyramidal neuron glutamatergic synapses of rat medial prefrontal cortex. In the present study, we examined detailed mechanisms of this DCG IV-induced LTD.

Long-term potentiation in rat prefrontal slices facilitated by phased application of dopamine.

We have previously shown that coupling bath application of dopamine with 50 Hz tetani induces long-term depression in rat prefrontal slices [Neuroscience 85 (1998) 669]. Here, we report a reliable protocol for inducing long-term potentiation in the same preparation. Long-term potentiation was induced by the same dopamine-tetani coupling protocol when the coupling was preceded (approximately 30 min) by a single bath application of dopamine.

Control of Ca(2+) influx by cannabinoid and metabotropic glutamate receptors in rat cerebellar cortex requires K(+) channels.

1. In the rodent cerebellum, both presynaptic CB1 cannabinoid receptors and presynaptic mGluR4 metabotropic glutamate receptors acutely depress excitatory synaptic transmission at parallel fibre-Purkinje cell synapses. Using rat cerebellar slices, we have analysed the effects of selective CB1 and mGluR4 agonists on the presynaptic Ca(2+) influx which controls glutamate release at this synapse.

Retrograde modulation of transmitter release by postsynaptic subtype 1 metabotropic glutamate receptors in the rat cerebellum.

1. The aim of the study was to elucidate the mechanisms underlying the depressant effect of the group I/II metabotropic glutamate receptor (mGluR) agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on parallel fibre (PF) to Purkinje cell (PC) synaptic transmission. Experiments were performed in rat cerebellar slices using the whole-cell patch-clamp technique and fluorometric measurements of presynaptic calcium variation 2.

Expression of protein kinase C inhibitor blocks cerebellar long-term depression without affecting Purkinje cell excitability in alert mice.

A longstanding but still controversial hypothesis is that long-term depression (LTD) of parallel fiber-Purkinje cell synapses in the cerebellum embodies part of the neuronal information storage required for associative motor learning. Transgenic mice in which LTD is blocked by Purkinje cell-specific inhibition of protein kinase C (PKC) (L7-PKCI mutants) do indeed show impaired adaptation of their vestibulo-ocular reflex, whereas the dynamics of their eye movement performance are unaffected. However, because L7-PKCI mutants have a persistent multiple climbing fiber innervation at least until 35 d of age and because the baseline discharge of the Purkinje cells in the L7-PKCI mutants is unknown, factors other than a blockage of LTD induction itself may underlie their impaired motor learning.

Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons.

Cannabinoids receptors have been reported to modulate synaptic transmission in many structures of the CNS, but yet little is known about their role in the prefrontal cortex where type I cannabinoid receptor (CB-1) are expressed. In this study, we tested first the acute effects of selective agonists and antagonist of CB-1 on glutamatergic excitatory postsynaptic currents (EPSCs) in slices of rat prefrontal cortex (PFC). EPSCs were evoked in patch-clamped layer V pyramidal cells by stimulation of layer V afferents.

Dopamine receptors and groups I and II mGluRs cooperate for long-term depression induction in rat prefrontal cortex through converging postsynaptic activation of MAP kinases.

Tetanic stimuli to layer I-II afferents in rat prefrontal cortex induced long-term depression (LTD) of layer I-II to layer V pyramidal neuron glutamatergic synapses when tetani were coupled to bath application of dopamine. This LTD was blocked by the following metabotropic glutamate receptor (mGluR) antagonists coapplied with dopamine: (S)-alpha-methyl-4-carboxyphenylglycine (MCPG; group I and II antagonist), (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; group I antagonist), or (RS)-alpha-methylserine-O-phosphate monophenyl ester (MSOPPE; group II antagonist). This suggests that the dopamine-facilitated LTD requires synaptic activation of groups I and II mGluRs during tetanus.

Inositol-1,4,5-trisphosphate-mediated rescue of cerebellar long-term depression in subtype 1 metabotropic glutamate receptor mutant mouse.

Recent reports have outlined that cerebellar long-term depression requires the activation of subtype 1 metabotropic glutamate receptors, since long-term depression is impaired in subtype 1 metabotropic glutamate receptor (mGluR1) knockout mice. In order to better define the role of mGluR1-activated signal transduction pathways, we attempted to rescue cerebellar long-term depression in mGluR1 knockout mice by direct activation of subsequent intracellular cascades. The present results demonstrate that the inositol-1,4,5-trisphosphate signal transduction pathway remains functional in mGluR1 knockout mice, that calcium release from internal stores evoked by the combined photolytic release of inositol- 1,4,5-trisphosphate/pairing protocol is sufficient to rescue long-term depression in these mutants, and that this long-term depression is sensitive to a protein kinase C inhibitor.

Cellular mechanisms of cerebellar LTD.

In the past decade there have been advances in understanding the cellular mechanisms of the long-term depression (LTD) of synaptic transmission at parallel fiber-Purkinje cell synapses in the cerebellum. This review first summarizes current views on mechanisms involved in LTD induction, from activation of voltage-gated Ca2+ channels, of ionotropic (AMPA) and metabotropic (mGluRI) glutamate receptors, to stimulation of protein kinase C and nitric oxide formation. Second, we will focus on recent findings that point towards the involvement of Ca2+ release from internal stores in LTD induction, localize the sources and targets of nitric oxide and indicate a postsynaptic site for LTD expression.

Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells.

1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic transmission and synaptic plasticity.

Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex.

Using sharp-electrode intracellular recordings, we studied the dopaminergic facilitation of synaptic plasticity in layer I-II afferents--layer V neuron glutamatergic synapses in rat prefrontal cortex in vitro. Tetanic stimulation (100 pulses at 50 Hz, four times at 0.1 Hz) to layer I-II afferents induced N-methyl-D-aspartate receptor-independent long-term depression (>40 min) of the glutamatergic synapses when the stimulation was coupled with a bath-application of dopamine.

Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited.

Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses in the cerebellum has been the first established example of enduring decrease of synaptic efficacy in the central nervous system. This review focuses on the underlying cellular and molecular mechanisms. Thus, at the level of the postsynaptic membranes of PCs, induction of LTD requires concommitent activation of voltage-gated calcium channels (VGCCs) and of ionotropic and metabotopic glutamate receptors, of the alpha-amino-3 hydroxy-5-methyl-isoxalone-4-propionate (AMPA) and mGluR1 alpha types respectively.

staggerer phenotype in retinoid-related orphan receptor alpha-deficient mice.

Retinoid-related orphan receptor alpha (RORalpha) is a member of the nuclear receptor superfamily. To study its physiological role we generated null-mutant mice by targeted insertion of a lacZ reporter gene encoding the enzyme beta-galactosidase. In heterozygous RORalpha+/- mice we found beta-galactosidase activity, indicative of RORalpha protein expression, confined to the central nervous system, skin and testis.