Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain.

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs.

Perineuronal nets are under the control of type-5 metabotropic glutamate receptors in the developing somatosensory cortex.

mGlu5 metabotropic glutamate receptors are highly functional in the early postnatal life, and regulate developmental plasticity of parvalbumin-positive (PV) interneurons in the cerebral cortex. PV cells are enwrapped by perineuronal nets (PNNs) at the closure of critical windows of cortical plasticity. Changes in PNNs have been associated with neurodevelopmental disorders.

A summary on cutting edge advancements in sterilization and cleaning technologies in medical, food, and drug industries, and its applicability to spacecraft hardware.

Issued primarily by COSPAR (the Committee On SPAce Research), international Planetary Protection Policies mandate that all spacecraft hardware in contact with extraterrestrial environments "of chemical evolution and/or origin of life interest and for which scientific opinion provides a significant chance of contamination which could compromise future investigations" (Kminek and Rummel, 2015) undergo biological burden control processes. These policies seek to limit the (forward) biological contamination of the target body by terrestrial microorganisms on the spacecraft, so that future missions to the target body will provide accurate and reliable scientific results. Also, these policies seek to prevent the (backward) biological contamination of the Earth by a sample returned from the target body.

Serum 25-hydroxy vitamin D levels in essential hypertension.

Vitamin D may have prognostic value in hypertension patients and, in addition to conventional biomarkers, could be a valuable tool for disease management. The aim of this study was to assess the association of vitamin D status in patients with essential hypertension and to evaluate its prognostic utility. Forty-eight consecutive patients (40 Caucasian and 8 Asian) aged between 30 and 80 years (mean 61.

Rusty Microglia: Trainers of Innate Immunity in Alzheimer's Disease.

Alzheimer's disease, the most common form of dementia, is marked by progressive cognitive and functional impairment believed to reflect synaptic and neuronal loss. Recent preclinical data suggests that lipopolysaccharide (LPS)-activated microglia may contribute to the elimination of viable neurons and synapses by promoting a neurotoxic astrocytic phenotype, defined as A1. The innate immune cells, including microglia and astrocytes, can either facilitate or inhibit neuroinflammation in response to peripherally applied inflammatory stimuli, such as LPS.

mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors.

In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable.

Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain.

Background L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.

The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?

Background: Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The α2δ subunit is a component of high voltage-activated VSCCs (i.

Sinonasal adenocarcinoma in a patient without exposure to risk factors Case report and review of the literature.

Objective: Sinonasal adenocarcinoma is a tumor typically associated with exposure to occupational carcinogens. The International Agency for Research on Cancer (IARC) published several data in order to classify carcinogenic power of physical-chemical agents as far as sinonasal cancer is concerned.

Materials And Methods: We report a clinical case of sinonasal adenocarcinoma observed in an 84 years old patient, without clinical history of past exposure to carcinogens, smoke and alcohol.

Expression of the K/Cl cotransporter, KCC2, in cerebellar Purkinje cells is regulated by group-I metabotropic glutamate receptors.

The neuronal K/Cl symporter, KCC2, shapes synaptic responses mediated by Cl-permeant GABA receptors. Moving from the evidence that excitatory neurotransmission drives changes in KCC2 expression in cerebellar neurons, we studied the regulation of KCC2 expression by group-I metabotropic glutamate (mGlu) receptors in the cerebellum of adult mice. Mice lacking mGlu5 receptors showed a large reduction in cerebellar KCC2 protein levels and a loss of KCC2 immunoreactivity in Purkinje cells.

Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia.

The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS.

Proteomic and epigenomic markers of sepsis-induced delirium (SID).

In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010).

Delirium from the gliocentric perspective.

Delirium is an acute state marked by disturbances in cognition, attention, memory, perception, and sleep-wake cycle which is common in elderly. Others have shown an association between delirium and increased mortality, length of hospitalization, cost, and discharge to extended stay facilities. Until recently it was not known that after an episode of delirium in elderly, there is a 63% probability of developing dementia at 48 months compared to 8% in patients without delirium.

Changes in the expression of genes encoding for mGlu4 and mGlu5 receptors and other regulators of the indirect pathway in acute mouse models of drug-induced parkinsonism.

Neuroadaptive changes involving the indirect pathway of the basal ganglia motor circuit occur in the early phases of parkinsonism. The precise identification of these changes may shed new light into the pathophysiology of parkinsonism and better define the time window of pharmacological intervention. We examined some of these changes in mice challenged with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or with the dopamine receptor blocker, haloperidol.

Metabotropic glutamate receptors as drug targets: what's new?

The question in the title: 'what's new?' has two facets. First, are 'clinical' expectations met with success? Second, is the number of CNS disorders targeted by mGlu drugs still increasing? The answer to the first question is 'no', because development program with promising drugs in the treatment of schizophrenia, Parkinson's disease, and Fragile X syndrome have been discontinued. Nonetheless, we continue to be optimistic because there is still the concrete hope that some of these drugs are beneficial in targeted subpopulations of patients.

Analgesic effect of a single preoperative dose of the antibiotic ceftriaxone in humans.

Unlabelled: Repeated injections of the antibiotic ceftriaxone cause analgesia in rodents by upregulating the glutamate transporter, GLT-1. No evidence is available in humans. We studied the effect of a single intravenous administration of ceftriaxone in patients undergoing decompressive surgery of the median or ulnar nerves.

N-Acetyl-cysteine causes analgesia by reinforcing the endogenous activation of type-2 metabotropic glutamate receptors.

Background: Pharmacological activation of type-2 metabotropic glutamate receptors (mGlu2 receptors) causes analgesia in experimental models of inflammatory and neuropathic pain. Presynaptic mGlu2 receptors are activated by the glutamate released from astrocytes by means of the cystine/glutamate antiporter (System x(c)(-) or Sx(c)(-)). We examined the analgesic activity of the Sx(c)(-) activator, N-acetyl-cysteine (NAC), in mice developing inflammatory or neuropathic pain.

Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons.

We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH(+)) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl-p-tyrosine (αMpT, 150 mg/kg, i.p.

Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress.

Epidemiological studies suggest that emotional liability in infancy could be a predictor of anxiety-related disorders in the adulthood. Rats exposed to prenatal restraint stress ("PRS rats") represent a valuable model for the study of the interplay between environmental triggers and neurodevelopment in the pathogenesis of anxious/depressive like behaviours. Repeated episodes of restraint stress were delivered to female Sprague-Dawley rats during pregnancy and male offspring were studied.

Role of the intravitreal growth factors in the pathogenesis of idiopathic epiretinal membrane.

Purpose: The aim of the present study is to evaluate the roles of TGFs β1 and β2, glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) in the pathogenesis of idiopathic epiretinal membrane (ERM).

Methods: Eight patients, six males and two females, with an average age of 60.25 ± 17.

The conditioned eyeblink reflex: a potential tool for the detection of cerebellar dysfunction in multiple sclerosis.

The delayed conditioned eyeblink reflex, in which an individual learns to close the eyelid in response to a conditioned stimulus (e.g. a tone) relies entirely on the functional integrity of a cerebellar motor circuitry that involves the contingent activation of Purkinje cells by parallel and climbing fibres.

Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1), an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway.