Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling.

Recent studies have shown that the gut microbiome changes brain function, behavior, and psychiatric and neurological disorders. The Gut-Brain Axis (GBA) provides a neuronal pathway to explain this. But exactly how do commensal bacteria signal through the epithelial layer of the large intestine to activate GBA nerve afferents? An in vitro model is described.

Evaluation of Microbiota and Weight Alterations After the Administration of Tetracycline and Lactobacillus gasseri in Rats.

Obesity is one of the largest current public health problems. Recent studies suggest that persistent changes in the intestinal microbiota (dysbiosis) can eventually lead to obesity. A stable core of intestinal microbiota exists, primarily composed of the phyla Firmicutes and Bacteroidetes, but their proportions can be altered by antibiotics.

Altered plasma levels of arginine metabolites in depression.

L-Arginine pathway metabolites appear to play differential roles in the pathogenesis of major depressive disorder (MDD). Studies have revealed an antidepressant and anxiolytic effect of agmatine and putrescine. Possible mechanisms of these effects include inhibition of nitric oxide synthase and N-methyl-D-aspartate receptors.

Agmatine: clinical applications after 100 years in translation.

Agmatine (decarboxylated arginine) has been known as a natural product for over 100 years, but its biosynthesis in humans was left unexplored owing to long-standing controversy. Only recently has the demonstration of agmatine biosynthesis in mammals revived research, indicating its exceptional modulatory action at multiple molecular targets, including neurotransmitter systems, nitric oxide (NO) synthesis and polyamine metabolism, thus providing bases for broad therapeutic applications. This timely review, a concerted effort by 16 independent research groups, draws attention to the substantial preclinical and initial clinical evidence, and highlights challenges and opportunities, for the use of agmatine in treating a spectrum of complex diseases with unmet therapeutic needs, including diabetes mellitus, neurotrauma and neurodegenerative diseases, opioid addiction, mood disorders, cognitive disorders and cancer.

Putative agmatinase inhibitor for hypoxic-ischemic new born brain damage.

Agmatine is an endogenous brain metabolite, decarboxylated arginine, which has neuroprotective properties when injected intraperitoneally (i.p.) into rat pups following hypoxic-ischemia.

Database of genetic studies of bipolar disorder.

This study describes the construction and preliminary analysis of a database of summary level genetic findings for bipolar disorder from the literature. The database is available for noncommercial use at http://bioprogramming.bsd.

Pro-inflammatory biomakers in depression: treatment with venlafaxine.

High levels of pro-inflammatory biomarkers have been reported in depression. In the present study, five pro-inflammatory biomarkers were measured in the blood of patients with major depressive disorder (MDD). Biomarker levels were compared to age- and sex-matched healthy subjects.

Platelet imidazoline receptors as state marker of depressive symptomatology.

Objective: Previous studies have shown that imidazoline receptors (IR-1) are increased in platelets and frontal cortex of depressed patients, and this up-regulation is normalized (down-regulated) after antidepressant drug treatments. It has been hypothesized that IR-1 up-regulation during the depressive episode may be a state marker for depressive symptomatology. The goal of the present study was to address the state versus trait question.

Relationship between platelet imidazoline receptor-binding peptides and candidate imidazoline-1 receptor, IRAS.

A candidate human imidazoline-1 receptor, designated imidazoline receptor antisera-selected (IRAS) protein, was cloned based on immunoreactivity with antiserum against a purified imidazoline receptor binding peptide (IRBP antiserum). Human IRAS is 167 kD in size, different from 33- to 85-kD IRBP bands previously linked to the human platelet I(1) receptor. To explore the possible relationship between IRAS and these smaller proteins, seven different epitope-specific antisera against IRAS were raised in rabbits for comparison with IRBP antiserum.

Intracellular effect of imidazoline receptor on alpha(2A)-noradrenergic receptor.

Imidazoline-1 receptors (I(1)R) and alpha(2)-noradrenergic receptors (alpha(2)AR) are known to coexist in many cell types and bind many of the same imidazoline ligands. Herein, the possibility of an interaction between these receptors was explored using a cloned cDNA that encodes a protein with I(1)R-like binding properties, designated imidazoline receptor antisera-selected (IRAS). Chinese hamster ovary (CHO) sublines permanently expressing the human subtype alpha(2A)AR cDNA were transiently cotransfected with the human IRAS cDNA (pIRAS).

IRAS is an anti-apoptotic protein.

Active cell death, also known as apoptosis, has been implicated in the pathophysiology of diseases such as cancer, heart failure and neurodegenerative disorders. We report the anti-apoptotic function of IRAS, which was previously shown to bind imidazoline ligands. The amino acid sequence of human IRAS (hIRAS) is unrelated to known proteins, except for rat IRAS and a mouse homologue named nischarin, which binds the alpha5 integrin subunit of the fibronectin receptor.

Is agmatine an endogenous factor against stress?

Agmatine is an endogenous amine synthesized from the decarboxylation of arginine. A proposed intracellular role of agmatine is to balance the production of polyamines (a promitotic process) and nitric oxide (an inflammatory process). Agmatine is also released from neurons upon depolarization.

Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine.

Agmatine, an amine formed by decarboxylation of L-arginine by arginine decarboxylase (ADC), has been recently discovered in mammalian brain and other tissues. While the cloning and sequencing of ADC from plant and bacteria have been reported extensively, the structure of mammalian enzyme is not known. Using homology screening approach, we have identified a human cDNA clone that exhibits ADC activity when expressed in COS-7 cells.

Effect of agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cells.

Aims: Agmatine is an endogenous guanido amine and has been shown to be neuroprotective in vitro and in vivo. The aims of this study are to investigate whether agmatine is protective against cell death induced by different agents in cultured neurons and PC12 cells.

Methods: Cell death in neurons, cultured from neonatal rat cortex, was induced by incubating with (a) NMDA (100 microM) for 10 min, (b) staurosporine (protein kinase inhibitor, 100 nM) for 24 h, and (c) calcimycin (calcium ionophore, 100 nM) for 24 h in the presence and absence of agmatine (1 micro M to 1 mM).

Differential expression of alpha2-adrenoceptor vs. imidazoline binding sites in postmortem orbitofrontal cortex and amygdala of depressed subjects.

Clonidine is a well established antihypertensive agent that is also used effectively to treat a variety of psychiatric disorders. Clonidine is a prototypic imidazoline compound that acts as an alpha(2)-adrenergic agonist but possesses nearly equivalent affinity for non-adrenergic imidazoline binding sites (I-sites). Receptor autoradiography of [(3)H]-clonidine binding presented herein compares densities of alpha(2)-adrenoceptors and I-sites (under a noradrenergic-mask) in Brodmann's area 47 of the left orbitofrontal cortex (OFC) and in six amygdaloid nuclei of subjects with major depression (n=12) vs.

Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses.

Moxonidine is a centrally-active imidazoline compound with preferential affinity for imidazoline receptors (IR) over alpha(2)-adrenoceptors (alpha(2)AR). Clinically, moxonidine has proven advantageous for treating hypertension over pure alpha(2)-adrenergic agonists (i.e.

Imidazoline receptors: possible involvement in the pathophysiology and treatment of depression.

Imidazoline receptors (IR), a novel family of non-adrenergic receptors, are present in brain, especially the limbic system, and platelets among other organs. Their functions include central mediation of blood pressure control and possibly modulation of affective symptomatology. Studies of unipolar depressed patients have revealed consistent up-regulation of the I(1) subtype on the platelet.

Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats.

Nitric oxide and excitatory amino acids contribute to hypoxic-ischemic brain injury. Agmatine, an endogenous neurotransmitter or neuromodulator, is an inhibitor of nitric oxide synthase and an antagonist of N-methyl-D-aspartate receptors. Does agmatine reduce brain injury in the rat pup hypoxic-ischemic model? Seven-day old rat pups had right carotid arteries ligated followed by 2.