TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis.

The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition.

Nestin Regulates Neurogenesis in Mice Through Notch Signaling From Astrocytes to Neural Stem Cells.

The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes-/-) mice. We found that the proliferation of Nes-/- neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes-/- mice was increased.

Lactobacillus rhamnosusGG reduces hepatic fibrosis in a model of chronic liver disease in rats.

Background: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver.

Aim: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats.

Methods: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).

The Glutamine Transporters and Their Role in the Glutamate/GABA-Glutamine Cycle.

Glutamine is a key amino acid in the CNS, playing an important role in the glutamate/GABA-glutamine cycle (GGC). In the GGC, glutamine is transferred from astrocytes to neurons, where it will replenish the inhibitory and excitatory neurotransmitter pools. Different transporters participate in this neural communication, i.

Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs due to acute and chronic liver diseases, the hallmark of which is the increased levels of ammonia and subsequent alterations in glutamine synthesis, i.e. conditions associated with the pathophysiology of HE.

Effects of hyperammonemia on brain energy metabolism: controversial findings in vivo and in vitro.

The literature related to the effects of elevated plasma ammonia levels on brain energy metabolism is abundant, but heterogeneous in terms of the conclusions. Thus, some studies claim that ammonia has a direct, inhibitory effect on energy metabolism whereas others find no such correlation. In this review, we discuss both recent and older literature related to this controversial topic.

Expression of Glutamate Decarboxylase (GAD) mRNA in the brain of bile duct ligated rats serving as a model of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neurologic disorder that involves different pathophysiological mechanisms, including disturbances in the GABAergic neurotransmitter system. Albeit an overall increase in the level of neurotransmitter GABA has not been found in HE, alterations in GABA receptors and metabolism have been described. Moreover, it has been reported that bile duct ligated (BDL) rats, an animal model for the study of HE, exhibited an altered GABA biosynthesis involving preferentially the tricarboxylic (TCA) cycle.

Impairment of short term memory in rats with hepatic encephalopathy due to bile duct ligation.

Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to cognitive deficits. Different animal models for the study of HE have demonstrated learning and memory impairment and a number of neurotransmitter systems have been proposed to be involved in this. Recently, it was described that bile duct-ligated (BDL) rats exhibited altered spatio-temporal locomotor and exploratory activities and biosynthesis of neurotransmitter GABA in brain cortices.

Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats.

Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different rat models.

Inhibition of glutamine synthesis induces glutamate dehydrogenase-dependent ammonia fixation into alanine in co-cultures of astrocytes and neurons.

It has been previously demonstrated that ammonia exposure of neurons and astrocytes in co-culture leads to net synthesis not only of glutamine but also of alanine. The latter process involves the concerted action of glutamate dehydrogenase (GDH) and alanine aminotransferase (ALAT). In the present study it was investigated if the glutamine synthetase (GS) inhibitor methionine sulfoximine (MSO) would enhance alanine synthesis by blocking the GS-dependent ammonia scavenging process.

Synthesis of neurotransmitter GABA via the neuronal tricarboxylic acid cycle is elevated in rats with liver cirrhosis consistent with a high GABAergic tone in chronic hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric complication to liver disease. It is known that ammonia plays a role in the pathogenesis of HE and disturbances in the GABAergic system have been related to HE. Synthesis of GABA occurs by decarboxylation of glutamate formed by deamidation of astrocyte-derived glutamine.

Distinctive effects of unpredictable subchronic stress on memory, serum corticosterone and hippocampal BDNF levels in high and low exploratory mice.

Stress affects learning and memory processes and sensitivity to stress greatly varies between individuals. We studied behavioral and neurobiological effects of unpredictable subchronic stress (USCS) in two behavioral extremes of mice from the same strain (CF1) selected by their exploratory behavior of the central arena of an open field. The top and bottom 25% explorers were classified as low exploratory (LE) and high exploratory (HE) mice, respectively.

Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia.

Spinal mechanisms of antinociceptive action caused by guanosine in mice.

It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that intracerebroventricular (i.c.

Interleukin-6 serum levels in patients with Parkinson's disease.

Several lines of evidence suggest that neuroimmune mechanisms may be involved in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) is increased in the nigrostriatal region and in the cerebrospinal fluid of patients with PD. IL-6 serum level was evaluated in PD patients.

Demonstration of neuron-glia transfer of precursors for GABA biosynthesis in a co-culture system of dissociated mouse cerebral cortex.

Co-cultures of neurons and astrocytes were prepared from dissociated embryonic mouse cerebral cortex and cultured for 7 days. To investigate if these cultures may serve as a functional model system to study neuron-glia interaction with regard to GABA biosynthesis, the cells were incubated either in media containing [U-(13)C]glutamine (0.1, 0.

Antinociceptive effects of intracerebroventricular administration of guanine-based purines in mice: evidences for the mechanism of action.

It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines (GBPs) on pain transmission. The aim of this study was to investigate the effects of intracerebroventricular (i.

Pentylenetetrazol kindling alters adenine and guanine nucleotide catabolism in rat hippocampal slices and cerebrospinal fluid.

Pentylenetetrazol (PTZ) is commonly used as a convulsant drug. The enhanced seizure susceptibility induced by kindling is probably attributable to plastic changes in the synaptic efficacy. Adenosine and guanosine act both as important neuromodulators and neuroprotectors with mostly inhibitory effects on neuronal activity.

Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar patients during manic episode.

Background: Bipolar disorder (BD) has been increasingly associated with abnormalities in neuroplasticity and cellular resilience. Brain Derived Neurotrophic Factor (BDNF) gene has been considered an important candidate marker for the development of bipolar disorder and this neurotrophin seems involved in intracellular pathways modulated by mood stabilizers. Also, previous studies demonstrated a role for BDNF in the pathophysiology and clinical presentation of mood disorders.

Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics.

Neurotrophic factors regulate neuronal development and synaptic plasticity, possibly playing a role in the pathophysiology of schizophrenia and other psychiatric disorders. Decreased brain-derived neurotrophic factor (BDNF) levels have been found in brains and in the serum of schizophrenic patients, but results are inconsistent. Also, clozapine may upregulate brain BDNF expression.

Acute and chronic electroconvulsive shock in rats: effects on peripheral markers of neuronal injury and glial activity.

Electroconvulsive therapy is considered one of the most effective treatments of major depression, but controversy still exists on whether it may be brain damaging. The aim of this work was to evaluate the cerebrospinal fluid (CSF) levels of neuron specific enolase (NSE), protein S100B and lactate of rats submitted to acute and chronic models of ECS. Rats were submitted to either one shock (acute) or a series of eight shocks, applied one at every 48 h (chronic).

Biochemical brain markers and purinergic parameters in rat CSF after seizure induced by pentylenetetrazol.

Cellular and molecular mechanisms involved in the generation of seizures and the magnitude of neural cells injury are not fully understood. We evaluated astrocyte and/or neuronal injury in rats in the pentylenetetrazol model of acute seizures by measuring S100B and NSE levels in cerebrospinal fluid. Additionally, we determined ADP and GDP hydrolysis by soluble nucleoside triphosphate diphosphohydrolase in the cerebrospinal fluid, and the concentration of nucleosides adenosine, inosine and guanosine as putative markers of brain injury.