Comment on "Perturbation theory of scattering for grazing-incidence fast-atom diffraction", by W. Allison, S. Miret-Artés and E. Pollak, , 2022, , 15851.

In this comment we discuss some aspects of , 2022, , 15851, by Allison , an article intensely motivated by our study of grazing incidence fast atom diffraction (GIFAD) for He-KCl(001) [G. A. Bocan, H.

Diazepam-Induced Down-Regulation of the GABA receptor α1 Subunit, as mediated by the activation of L-Type Voltage-Gated calcium Channel/Ca/Protein kinase a signaling cascade.

Benzodiazepines are among the most prescribed drug class worldwide to treat disorders such as anxiety, insomnia, muscle spasticity, and convulsive disorders, and to induce presurgical sedation. Although benzodiazepines exhibit a high therapeutic index and low toxicity in short-term treatments, prolonged administration induces tolerance to most of their therapeutic actions. The mechanism of this tolerance remains unclear.

Grazing incidence fast atom and molecule diffraction: theoretical challenges.

This perspective article reviews the state-of-the-art of grazing incidence fast atom and molecule diffraction (GIFAD and GIFMD) simulations and addresses the main challenges that theorists, aiming to provide useful inputs in this topic, are facing. We first discuss briefly the methods used to build accurate potential energy surfaces describing the interaction between the projectile and the surface. Subsequently, we focus on the dynamics simulation methods for GIFAD, a phenomenon that has received a lot of experimental attention since 2007, when the first measurements were published.

Regulation of GABA Receptors Induced by the Activation of L-Type Voltage-Gated Calcium Channels.

GABA receptors are pentameric ion channels that mediate most synaptic and tonic extrasynaptic inhibitory transmissions in the central nervous system. There are multiple GABA receptor subtypes constructed from 19 different subunits in mammals that exhibit different regional and subcellular distributions and distinct pharmacological properties. Dysfunctional alterations of GABA receptors are associated with various neuropsychiatric disorders.

Anomalous KCl(001) Surface Corrugation from Fast He Diffraction at Very Grazing Incidence.

We present theoretical and experimental evidence of an anomalous surface corrugation behavior in He-KCl(001) for incidence along ⟨110⟩. When the He normal energy decreases below 100 meV, i.e.

Benzodiazepine exposure induces transcriptional down-regulation of GABA receptor α1 subunit gene via L-type voltage-gated calcium channel activation in rat cerebrocortical neurons.

GABA receptors are targets of different pharmacologically relevant drugs, such as barbiturates, benzodiazepines, and anesthetics. In particular, benzodiazepines are prescribed for the treatment of anxiety, sleep disorders, and seizure disorders. Benzodiazepines potentiate GABA responses by binding to GABA receptors, which are mainly composed of α (1-3, 5), β2, and γ2 subunits.

Spot-beam effect in grazing atom-surface collisions: from quantum to classical.

Grazing incidence fast atom diffraction (GIFAD) is a sensitive tool for surface analysis, which strongly relies on the quantum coherence of the incident beam. In this article we study the spot-beam effect, due to contributions coming from different positions of the focus point of the incident particles, which affects the coherence of GIFAD spectra. We show that the influence of the spot-beam effect on GIFAD patterns depends on the width of the surface area that is coherently lighted by the atomic beam.

Regulation of GABA receptors by prolonged exposure to endogenous and exogenous ligands.

GABA receptors mediate most of the fast inhibitory transmissions in the central nervous system. These receptors are pentameric complexes that exhibit high structural and pharmacological heterogeneity, as they can be constructed from 19 distinct subunits. GABA receptors are the targets of numerous clinically relevant drugs used to treat various disorders such as anxiety, insomnia and epilepsy.

Activation-induced regulation of GABAA receptors: Is there a link with the molecular basis of benzodiazepine tolerance?

Benzodiazepines have been used clinically for more than 50 years to treat disorders such as insomnia, anxiety, and epilepsy, as well as to aid muscle relaxation and anesthesia. The therapeutic index for benzodiazepines if very high and the toxicity is low. However, their usefulness is limited by the development of either or both tolerance to most of their pharmacological actions and dependence.

Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex.

The clinical use of benzodiazepines is limited by the development of tolerance to their pharmacological effects. Tolerance to each of the pharmacological actions of benzodiazepines develops at different rates. The aim of this work was to investigate the mechanism of tolerance by performing behavioral tests in combination with biochemical studies.

Working memory training triggers delayed chromatin remodeling in the mouse corticostriatothalamic circuit.

Working memory is a cognitive function serving goal-oriented behavior. In the last decade, working memory training has been shown to improve performance and its efficacy for the treatment of several neuropsychiatric disorders has begun to be examined. Neuroimaging studies have contributed to elucidate the brain areas involved but little is known about the underlying cellular events.

GABA-induced uncoupling of GABA/benzodiazepine site interactions is associated with increased phosphorylation of the GABAA receptor.

The use-dependent regulation of the GABAA receptor occurs under physiological, pathological, and pharmacological conditions. Tolerance induced by prolonged administration of benzodiazepines is associated with changes in GABAA receptor function. Chronic exposure of neurons to GABA for 48 hr induces a downregulation of the GABAA receptor number and an uncoupling of the GABA/benzodiazepine site interactions.

GABA-induced uncoupling of GABA/benzodiazepine site interactions is mediated by increased GABAA receptor internalization and associated with a change in subunit composition.

Persistent activation of GABAA receptors triggers compensatory changes in receptor function that are relevant to physiological, pathological and pharmacological conditions. Chronic treatment of cultured neurons with GABA for 48h has been shown to produce a down-regulation of receptor number and an uncoupling of GABA/benzodiazepine site interactions with a half-time of 24-25h. Down-regulation is the result of a transcriptional repression of GABAA receptor subunit genes and depends on activation of L-type voltage-gated calcium channels.

Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes.

Disruption of the GABAergic system has been implicated in multiple developmental disorders, including epilepsy, autism spectrum disorder and schizophrenia. The human gene encoding uPAR (PLAUR) has been shown recently to be associated with the risk of autism. The uPAR(-/-) mouse exhibits a regionally-selective reduction in GABAergic interneurons in frontal and parietal regions of the cerebral cortex as well as in the CA1 and dentate gyrus subfields of the hippocampus.

Pharmacological Properties of DOV 315,090, an ocinaplon metabolite.

Background: Compounds targeting the benzodiazepine binding site of the GABAA-R are widely prescribed for the treatment of anxiety disorders, epilepsy, and insomnia as well as for pre-anesthetic sedation and muscle relaxation. It has been hypothesized that these various pharmacological effects are mediated by different GABAA-R subtypes. If this hypothesis is correct, then it may be possible to develop compounds targeting particular GABAA-R subtypes as, for example, selective anxiolytics with a diminished side effect profile.

Surface expression of GABAA receptors is transcriptionally controlled by the interplay of cAMP-response element-binding protein and its binding partner inducible cAMP early repressor.

The regulated expression of type A gamma-aminobutyric acid (GABA) receptor (GABA(A)R) subunit genes plays a critical role in neuronal maturation and synaptogenesis. It is also associated with a variety of neurological diseases. Changes in GABA(A) receptor alpha1 subunit gene (GABRA1) expression have been reported in animal models of epilepsy, alcohol abuse, withdrawal, and stress.

Selective anxiolysis produced by ocinaplon, a GABA(A) receptor modulator.

Benzodiazepines remain widely used for the treatment of anxiety disorders despite prominent, often limiting side effects including sedation, muscle relaxation, and ataxia. A compound producing a robust anxiolytic action comparable to benzodiazepines, but lacking these limiting side effects at therapeutic doses (an anxioselective agent), would represent an important advance in the treatment of generalized anxiety disorder, and perhaps other anxiety disorders. Here we report that the pyrazolo[1,5-a]-pyrimidine, ocinaplon, exhibits an anxioselective profile in both preclinical procedures and in patients with generalized anxiety disorder, the most common of the anxiety disorders.

GABA induces activity dependent delayed-onset uncoupling of GABA/benzodiazepine site interactions in neocortical neurons.

Changes in the function of type A gamma-aminobutyric acid receptors (GABA(A)Rs) are associated with neuronal development and tolerance to the sedative-hypnotic effects of GABA(A)R positive modulators. Persistent activation of GABA(A)Rs by millimolar concentrations of GABA occurs under physiological conditions as GABAergic fast-spiking neurons in neocortex and cerebellum exhibit basal firing rates of 5 to 50 Hz and intermittent rates up to 250 Hz, leaving a substantial fraction of synaptic receptors occupied persistently by GABA. Persistent exposure of neurons to GABA has been shown to cause a down-regulation of receptor number and an uncoupling of GABA/benzodiazepine (BZD) site interactions with a half-life of approximately 24 h.

Role of allopregnanolone on cerebellar granule cells neurogenesis.

The role of allopregnanolone on immature cerebellar granule cells (CGC) proliferation was studied. Allopregnanolone (0.1-1 microM) increased [(3)H]thymidine incorporation and cell number determined by neuronal counting and by an MTT colorimetric assay.

Differential expression of gamma-aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons.

gamma-Aminobutyric acid type B receptors (GABA(B)Rs) mediate both slow inhibitory synaptic activity in the adult nervous system and motility signals for migrating embryonic cortical cells. Previous papers have described the expression of GABA(B)Rs in the adult brain, but the expression and functional significance of these gene products in the embryo are largely unknown. Here we examine GABA(B)R expression from rat embryonic day 10 (E10) to E18 compared with adult and ask whether embryonic cortical neurons contain functional GABA(B)R.

The modulation of mitochondrial nitric-oxide synthase activity in rat brain development.

Different mitochondrial nitric-oxide synthase (mtNOS) isoforms have been described in rat and mouse tissues, such as liver, thymus, skeletal muscle, and more recently, heart and brain. The modulation of these variants by thyroid status, hypoxia, or gene deficiency opens a broad spectrum of mtNOS-dependent tissue-specific functions. In this study, a new NOS variant is described in rat brain with an M(r) of 144 kDa and mainly localized in the inner mitochondrial membrane.

Diazepam fails to potentiate GABA-induced chloride uptake and to produce anxiolytic-like action in aged rats.

The pharmacological response to benzodiazepines has been demonstrated to be different in aged individuals in comparison to adults. We studied the age-dependent changes in some of the in vitro and behavioral effects of diazepam in aged (24 months old) rats, comparing them to adults (3 months old). We evaluated the in vitro gamma-aminobutyric acid (GABA)-induced 36Cl- uptake and the diazepam potentiation of GABA-stimulated 36Cl- uptake in microsacs from cerebral cortex of both groups of animals.

Modulatory action of zinc on GABA(A) receptor complex during avian CNS development.

In the present work, we studied the effect of zinc on GABA(A) receptor complex at three developmental stages of chick optic lobe (embryonic day 14, post-hatching day 1, and adulthood), in order to investigate the role of this cation in central nervous system (CNS) functional maturation. It was demonstrated that zinc exerts an inhibitory modulation of both GABA binding and GABA-gated chloride flux in a concentration-dependent manner with maximal effects at 100 microM zinc concentration. Maximal inhibition was higher at the embryonic stage and declined thereafter, disclosing minimal values at the adult stage.