Abstract：
:Neurosteroids are modulators of several receptors and ion channels and are implicated in the pathophysiology of several neuropsychiatric diseases including hepatic encephalopathy (HE). The neurosteroid, allopregnanolone, a positive allosteric modulator of GABA(A) receptors, accumulates in the brains of HE patients where it can potentiate GABA(A) receptor-mediated responses. Attenuation of the effects of neurosteroids on GABA-ergic neurotransmission is therefore of interest for the management of HE. In the present study, we determined the effect of the benzodiazepine partial inverse agonist, Ro15-4513, and the benzodiazepine antagonist, flumazenil on modulation of the GABA(A) mediated chloride currents by allopregnanolone and on spontaneous synaptic activity in cultured hippocampal neurons using the patch-clamp technique. Allopregnanolone (0.03-0.3 microM), dose-dependently potentiated GABA-induced currents, an action significantly reduced by Ro15-4513 (10 microM). In contrast, flumazenil (10 microM) had no effect on the ability of allopregnanolone to potentiate GABA(A) currents but it blocked the effects of Ro15-4513. The frequency of spontaneous synaptic activity was significantly reduced in the presence of allopregnanolone (0.1 microM) from 1.5+/-0.7 to 0.1+/-0.04Hz. This action was partially reversed by Ro15-4513 (10 microM) but was not significantly influenced by flumazenil (10 microM). These findings suggest that the beneficial affects of Ro15-4513 in experimental HE result from attenuation of the effects of neurosteroids at GABA(A) receptors. Our results may provide a rational basis for the use of benzodiazepine inverse agonists in the management and treatment of hepatic encephalopathy in patients with liver failure.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Ahboucha S,Coyne L,Hirakawa R,Butterworth RF,Halliwell RFdoi
10.1016/j.neuint.2005.12.006subject
Has Abstractpub_date
2006-06-01 00:00:00pages
703-7issue
8eissn
0197-0186issn
1872-9754pii
S0197-0186(06)00006-4journal_volume
48pub_type
杂志文章abstract：:Many studies indicate that chronic stress and excessive stress hormone can cause an inflammatory response. Thioredoxin-interacting protein (Txnip) as an endogenous thioredoxin inhibitor suppresses thioredoxin-produced antioxidant effects. Txnip was also found to interact with nucleotide-binding oligomerization domain-...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2019.104564
更新日期：2019-12-01 00:00:00
abstract：:Receptors for transmitters, as varied as those expressed by neurons, have been described on primary astrocyte cultures prepared from new-born rats and mice. A variety of functional effects and considerable cell-to-cell and regional heterogeneity have been observed for such receptors in vitro. The various systems avail...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/0197-0186(94)00118-e
更新日期：1995-01-01 00:00:00
abstract：:Neurodegenerative disorders are strongly associated with oxidative stress, which is induced by reactive oxygen species including hydrogen peroxide (H₂O₂). Epidemiological studies have suggested that coffee may be neuroprotective, but the molecular mechanisms underlying this effect have not been clarified. In this stud...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2012.02.004
更新日期：2012-04-01 00:00:00
abstract：:This paper describes the background in experiment and theory on which present-day studies of the biochemistry of learning and memory are based. It then reviews specifically the use of passive avoidance training in the day-old chick as a model for the analysis of the cellular events associated with memory-formation. It...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(89)90055-7
更新日期：1989-01-01 00:00:00
abstract：:Marked age-related changes are noted in the neurotensin distribution of the human hippocampus. Different neuronal structures containing neurotensin are detected by immunohistochemistry during postnatal brain growth from birth to 4 years but no later. They are the neurotensin-immunoreactive pyramidal cells of the subic...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(89)90114-9
更新日期：1989-01-01 00:00:00
abstract：:The consequences of irreversibly-inhibiting D2 dopaminergic receptors on the expression of D1 and D2 dopamine receptor mRNAs and proenkephalin mRNA and on the levels of mu- and delta-opioid receptors in rat striatum were studied following single or repeated administration of the irreversibly-acting D2 dopamine recepto...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(94)90143-0
更新日期：1994-10-01 00:00:00
abstract：:Choline acetyltransferase activity was detected in extensively washed membranes prepared from rat and guinea pig synaptosomes. When these preparations were treated with the non-ionic detergent Triton X-114 and heated to 37 degrees C to cause phase separation, a significant percentage was found to associate with the de...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(88)90111-8
更新日期：1988-01-01 00:00:00
abstract：:The multidrug transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier endothelium where it effluxes a range of drug substrates, preventing their accumulation within the brain. P-gp has been studied extensively for 40 years because of its crucial role in the absorption, distribution, metabolism and el...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2016.05.005
更新日期：2016-09-01 00:00:00
abstract：:L-serine-O-sulphate is a member of a group of amino acids collectively called gliotoxins and is a substrate for the high affinity sodium-dependent glutamate transporters. Previous studies have shown that it is toxic to primary cultures of astrocytes but the mode of toxicity is unknown. The current study demonstrates t...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2005.12.004
更新日期：2006-06-01 00:00:00
abstract：:5,7-Dihydroxytryptamine (5,7-DHT) is a selective serotonergic neurotoxin by virtue of its selective uptake into 5-hydroxytryptamine neurons and its ability to undergo autoxidation. The mechanism by which 5,7-DHT induces neurodegenerative effects remains enigmatic. The mechanism of autoxidation of 5,7-DHT, which has be...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(88)90165-9
更新日期：1988-01-01 00:00:00
abstract：:This report describes the effects of endothelins (ET-1 and ET-3) on ion transport systems expressed on cultured rat brain capillary endothelial cells (RBEC) and includes investigation of pharmacological properties of ET receptors, their reactivity and induction of signal transduction pathways. ET-1 stimulated IP3 form...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(97)00018-1
更新日期：1997-10-01 00:00:00
abstract：:Unveiling the roles of distinct cell types in brain response to insults is a partially unsolved challenge and a key issue for new neuroreparative approaches. In vivo models are not able to dissect the contribution of residential microglia and infiltrating blood-borne monocytes/macrophages, which are fundamentally undi...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2014.01.008
更新日期：2014-01-01 00:00:00
abstract：:The coenzyme functions of the B vitamins in intermediatry metabolism are well established; nevertheless, for none of them is it possible to determine precisely the connection between the biochemical lesions associated with deficiency and the neurological consequences. Although there is convincing evidence of a neurosp...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(84)90072-x
更新日期：1984-01-01 00:00:00
abstract：:Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have been proposed to be involved in the pyridoxal-5'-phosphate (PLP)-dependent biosynthesis of taurin...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2015.08.013
更新日期：2015-11-01 00:00:00
abstract：:For elucidation of thyroid hormone-induced responsiveness of fish brain, various doses (0.012, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2 and 4 ?g/g) of triiodothyronine (T(3)) were injected in Singi fish, Heteropneustes fossilis (Bloch), for 3 consecutive days and the changes in cytosolic NADP-dependent malic enzyme (ME, EC 1...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(89)90036-3
更新日期：1989-01-01 00:00:00
abstract：:Classical synaptic functions are important and suitable to relatively fast and discretely localized processes, but the nonclassical receptorial functions may be providing revolutionary possibilities for dealing at the cellular level with many of the more interesting and seemingly intractable features of neural and cer...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2003.11.016
更新日期：2004-09-01 00:00:00
abstract：:Development of tissue structure and three-dimensional microenvironment is crucial for regeneration of axons in the peripheral nerve repair. In this study we aimed to evaluate the efficacy of nerve regeneration by using an acellular nerve allograft (ANA) injected with allogenic skin-derived precursor differentiated Sch...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2016.04.003
更新日期：2016-07-01 00:00:00
abstract：:In recent years there has been a great deal of research within the stem cell field which has led to the definition and classification of a range of stem cells from a plethora of tissues and organs. Stem cells, by classification, are considered to be pluri- or multipotent and have both self-renewal and multi-differenti...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2016.08.001
更新日期：2017-06-01 00:00:00
abstract：:Therapeutic hypothermia as a physical method to lower the brain temperature of patients has been widely used in clinics as an effective and necessary step during the treatment of acute brain injury or edema. However, due to limitations of the ocular structure, the application of hypothermia in retinal neuroprotection ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2019.03.006
更新日期：2019-06-01 00:00:00
abstract：:Phenylalanine and its phenyl metabolites produced a clear inhibition of chick brain mevalonate 5-pyrophosphate decarboxylase, while mevalonate kinase and mevalonate 5-phosphate kinase were not significantly affected. Phenolic derivatives produced a similar or higher inhibition than that found in the presence of phenyl...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(91)90182-d
更新日期：1991-01-01 00:00:00
abstract：:The sensitivity of [(3)H]GABA and [(3)H]muscimol high-affinity binding sites to physiological (Krebs-Ringer's bicarbonate) and non-physiological (Tris-citrate) buffers was examined using synaptosomal membranes from bovine retinas. The maximum number of sites (B(max)) for [(3)H]GABA was present when the tissue was assa...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(86)90167-1
更新日期：1986-01-01 00:00:00
abstract：:The rat retinal ganglion cell (RGC) line RGC-5 constitutes a widely used model for studying physiological processes in retinal cells. In this paper we investigated the expression of clock and immediately early genes, and calcium mediated responses to physiological stimuli in differentiated and mitotically active RGC-5...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2010.05.013
更新日期：2010-10-01 00:00:00
abstract：:A significant loss of dopamine was found in rat striatal slices incubated with 1-methyl-4-phenylpyridinium ion (MPP+) at a concentration of 2 microM or higher. The addition of 7-nitroindazole, a specific inhibitor of neuronal nitric oxide synthase (nNOS), prevented this effect on dopamine when the concentration of MPP...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(05)80006-3
更新日期：1998-07-01 00:00:00
abstract：:Purified synaptic vesicles were isolated from hog cerebral cortex by a rapid procedure consisting of homogenization of cerebral cortex slices in iso-osmotic sucrose, differential centrifugation and sucrose density-gradient centrifugation. The purity of the vesicles was evaluated both biochemically and morphologically....
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(83)90095-5
更新日期：1983-01-01 00:00:00
abstract：:Endoplasmic reticulum (ER) stress is linked to several neurological disorders, and neuronal injury cascades initiated by excessive ER stress are mediated, in part, via mitochondrial dysfunction. In the present study, we identified FAM3A as an important regulator of ER stress-induced cell death in neuronal HT22 cells. ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2016.02.010
更新日期：2016-03-01 00:00:00
abstract：:The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1-(13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After 1-h substrate infusion, the incorp...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(00)00106-6
更新日期：2001-04-01 00:00:00
abstract：:Ischemic neuronal injury is associated with several life- and vision-threatening diseases. Neuroprotection is essential in the treatment of these diseases. Here, we identified and characterized a novel peptide, FK18, from basic fibroblast growth factor (bFGF). We further assessed the neuroprotective effects of this pe...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2017.02.015
更新日期：2017-09-01 00:00:00
abstract：:Oxidatively damaged proteins and lipid peroxidation products have been shown to accumulate in the brain of neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis, and oxidized lipoprotein is considered to be toxic and neurodegenerative. However, the role of lipoprotein and its oxidized form in ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2014.02.005
更新日期：2014-03-01 00:00:00
abstract：:The relationship between acidosis and the metabolism of glutamine and glutamate was studied in cultured astrocytes. Acidification of the incubation medium was associated with an increased formation of aspartate from glutamate and glutamine. The rise of the intracellular content of aspartate was accompanied by a signif...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(99)00141-2
更新日期：2000-04-01 00:00:00
abstract：:Oxidative stress has for long been linked to the neuronal cell death in many neurodegenerative conditions. Conventional antioxidant therapies have been less effective in preventing neuronal damage caused by oxidative stress due to their inability to cross the blood brain barrier. Nanoparticle antioxidants constitute a...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2015.08.011
更新日期：2015-10-01 00:00:00
