Abstract：
:We previously reported that elevated pressure induces axonal swelling and facilitates the synthesis of the neurosteroid, allopregnanolone (AlloP), in the ex vivo rat retina. Exogenously applied AlloP attenuates the axonal swelling, suggesting that the neurosteroid plays a neuroprotective role against glaucomatous pressure-induced injuries, although mechanisms underlying neurosteroidogenesis have not been clarified. The aim of this study was to determine whether AlloP synthesis involves activation of translocator protein 18 kD (TSPO) and whether TSPO modulates pressure-induced retinal injury. Ex vivo rat retinas were exposed to various pressures (10, 35, or 75 mmHg) for 24 h. Expression of TSPO, 5α-reductase (5aRD), and AlloP was examined by quantitative real-time RT-PCR, ELISA, immunohistochemistry, and LC-MS/MS. We also examined the effects of TSPO ligands on AlloP synthesis and retinal damage. In this acute model, quantitative real-time RT-PCR and ELISA analyses revealed that elevated pressure facilitated TSPO expression. Similarly, these methods also detected enhanced 5aRD (mostly type II), which was observed in retinal ganglion cells (RGC) and the inner nuclear layer (INL). Atriol, a TSPO antagonist, suppressed pressure mediated AlloP synthesis and induced more severe histological changes in the inner retina when combined with elevated pressure. PK11195, a TSPO ligand that facilitates AlloP synthesis by itself, remarkably diminished pressure-mediated retinal degeneration. These results suggest that AlloP synthesis is induced by sequential activation of TSPO and 5aRD in an ex vivo glaucoma model, and that TSPO agonists may serve as potential therapeutic agents for the prevention of pressure-induced retinal damage.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Ishikawa M,Yoshitomi T,Covey DF,Zorumski CF,Izumi Ydoi
10.1016/j.neuropharm.2016.09.001subject
Has Abstractpub_date
2016-12-01 00:00:00pages
142-159eissn
0028-3908issn
1873-7064pii
S0028-3908(16)30376-8journal_volume
111pub_type
杂志文章abstract：:Tarantula Chilobrachys jingzhao is one of the most venomous species distributed in China. In this study, we have isolated and characterized a novel neurotoxin named Jingzhaotoxin-IX (JZTX-IX) from the venom of the tarantula. JZTX-IX is a C-terminally amidated peptide composed of 35 amino acid residues. The toxin shows...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.04.009
更新日期：2009-08-01 00:00:00
abstract：:The objective of this study was to compare nAChR-mediated neurotransmitter release from slices of rat striatum, frontal cortex and hippocampus following chronic (-)-nicotine (Nic) administration (tartrate salt, 2 mg/kg twice daily for 10 days). Binding studies were also conducted to measure changes in receptor density...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00166-1
更新日期：2002-10-01 00:00:00
abstract：:Rats were pretreated twice daily for six consecutive days with either saline or 1.0, 5.0, or 10.0 mg/kg (+)-amphetamine. On the following day, single-unit recording techniques were used to identify serotonin-containing neurons in the dorsal raphe nucleus (DRN). Pretreatment with amphetamine did not alter the mean spon...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90233-4
更新日期：1987-07-01 00:00:00
abstract：:Ifenprodil, which is clinically used as a cerebral vasodilator, inhibited rat brain type A (MAO-A) and type B (MAO-B) monoamine oxidase activity. It did not, however, affect rat lung semicarbazide-sensitive amine oxidase. The degree of inhibition of either form of MAO was not changed by 30 min preincubation of the enz...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90190-m
更新日期：1991-07-01 00:00:00
abstract：:The subtype-selectivity of racemic [(3)H]CP-101,606, a novel high-affinity NMDA receptor radioligand was determined using defined recombinant NMDA receptor subunits expressed in HEK 293 cells. [(3)H]CP-101,606 binds to adult rodent forebrain and NR1/NR2B receptors expressed in HEK 293 cells with K(D)=4.2 nM and 6.0 nM...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00191-5
更新日期：2002-03-01 00:00:00
abstract：:The effects of chronic treatment with haloperidol on [3H]PK 11195 binding and labelling of the peripheral-type benzodiazepine receptor (PBR) in the rat brain and peripheral tissues were investigated using an in vitro receptor binding technique. The intraperitoneal injection with haloperidol (0.3 or 1.0 mg/kg) for 21 d...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00040-8
更新日期：1996-01-01 00:00:00
abstract：:Simultaneous recordings of responses of substantia gelatinosa and deep dorsal horn neurones to thermal noxious cutaneous stimulation were made in spinalized cats anaesthetized with urethane/chloralose. Morphine, whether applied iontophoretically in the substantia gelatinosa (50-200 nA) or injected intravenously (1.0-1...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90270-8
更新日期：1983-01-01 00:00:00
abstract：:The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90171-k
更新日期：1992-03-01 00:00:00
abstract：:The aim of the present study was to evaluate functional changes of mGluR5 expression in advanced Alzheimer's disease (AD) using positron emission tomography (PET) with an mGluR5 specific radiotracer ([18F]FPEB) in 5xFAD AD model. Subsequently, in the same animal, mGluR5 expression was quantified by immunoassay techniq...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.02.003
更新日期：2018-05-01 00:00:00
abstract：:Activation of peroxisome proliferator-activated receptor beta/delta (PPAR-β/δ), a nuclear receptor acting as a transcription factor, was shown to be protective in various models of neurological diseases. However, there is no information about the role of PPAR-β/δ as well as its molecular mechanisms in neonatal hypoxia...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.08.003
更新日期：2018-09-15 00:00:00
abstract：:In PC12 cells, isosorbide dinitrate (ISDN) and S-nitrosol-acetyl-penicillamine (SNAP), both nitric oxide (NO) generators, attenuated K+ (56 mM)-stimulated release of dopamine. The attenuation was not observed with isosorbide, an ISDN analog lacking NO generating capacity. In this model, A23187 (Ca2+ ionophore), Bay K8...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00151-h
更新日期：1995-02-01 00:00:00
abstract：:Cholecystokinin octapeptide (CCK-8), caerulein and seven out of ten analogues of caerulein produced in mice, after subcutaneous administration, a dose-dependent drop in rectal temperature. For the hypothermic effect, i.e. a decrease in temperature by at least 1.5 degree C, ED50's were estimated with these peptides and...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90067-3
更新日期：1982-08-01 00:00:00
abstract：:Purine nucleotides, such as ATP and ADP, activate ionotropic P2X and metabotropic P2Y receptors to regulate neurotransmitter release in the peripheral as well as central nervous system. Here we report another type of ATP-induced presynaptic modulation of glutamate release in rat medullary dorsal horn neurons. Glutamat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.01.020
更新日期：2015-06-01 00:00:00
abstract：:Lesions of the ventral hippocampus (VH) in neonatal rats result in post-pubertal alterations in a number of cognitive, social and motor behaviors that bear some analogy to schizophrenia. Increased sensitivity to stress and psychostimulants and prefrontal functional changes in the lesioned animals suggest an involvemen...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.08.001
更新日期：2004-01-01 00:00:00
abstract：:Alterations in rapid eye movement sleep (REM) have been suggested as valid translational efficacy markers: activation of the metabotropic glutamate receptor 2 (mGluR2) was shown to increase REM latency and to decrease REM duration. The present paper addresses the effects on vigilance states of the mGluR2 positive allo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.11.031
更新日期：2016-04-01 00:00:00
abstract：:Long-term alcohol use causes widespread changes in gene expression in the human brain. Aberrant gene expression changes likely contribute to the progression from occasional alcohol use to alcohol use disorder (including alcohol dependence). Transcriptome studies have identified individual gene candidates that are link...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.02.017
更新日期：2017-08-01 00:00:00
abstract：:The present study used pharmacological and gene ablation techniques to examine the involvement of kappa opioid receptors (KOPr) in modulating the convulsant effects of two mechanistically different drugs: cocaine and pentylenetetrazol (PTZ; GABA-A receptor antagonist) in mice. Systemic administration of the selective ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.10.007
更新日期：2007-03-01 00:00:00
abstract：:Lithium has been reported to exert neuroprotective activity in several neuronal cell cultures and in vivo models against glutamate toxicity. Since this action was reported to be associated with alterations in the antiapoptotic Bcl-2 family proteins, the effect of chronic lithium diet on the ability of the parkinsonism...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.02.005
更新日期：2004-06-01 00:00:00
abstract：:A new in vivo pharmacological method for the quantitative evaluation of alpha 1-adrenoceptor agonists and antagonists has been developed. It consists of recording the myoclonic twitch activity (MTA) of the suprahyoideal muscle of rats anesthetized with urethane. In these animals, the isomers of amphetamine elicited my...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90175-9
更新日期：1986-05-01 00:00:00
abstract：:The present study measured oxygen consumption and core body temperature following central injections of bombesin (1.0 microgram) in food-deprived rats. Oxygen consumption did not differ for bombesin- and control-injected rats while mean core body temperature decreased significantly following bombesin administrations. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90060-1
更新日期：1984-11-01 00:00:00
abstract：:The role of the adenosine A(2A) receptor in the hypnotic effects of ethanol was assessed in mice. The duration of the loss of righting reflex following acute ethanol administration was shorter for A(2A) receptor-deficient mice (A(2A)R KO) than for wild-type mice (A(2A)R WT), whereas the fall in body temperature was no...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00254-5
更新日期：2003-12-01 00:00:00
abstract：:In general, N-methyl-D-aspartate (NMDA) receptor antagonists inhibit learning and long term potentiation (LTP). However, it has been suggested that direct tonic, i.e. non-temporal, activation of NMDA receptors, in contrast to learning, may lead to an increase in synaptic "noise" and, in turn, to a loss of association ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00070-1
更新日期：1997-07-01 00:00:00
abstract：:Depression is a common co-morbid condition most often observed in subjects with mild cognitive impairment (MCI) and during the early stages of Alzheimer's disease (AD). Dysfunction of the central noradrenergic nervous system is an important component in depression. In AD, locus coeruleus (LC) noradrenergic neurons are...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.09.003
更新日期：2016-02-01 00:00:00
abstract：:Postictal refractoriness may be taken as an expression of lasting activity of inhibitory systems arresting seizures. We tested drugs interfering with GABAergic inhibitory system in pairs of cortical epileptic afterdischarges induced with 1-min interval in rats. Under control conditions the second stimulation failed to...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.09.007
更新日期：2015-01-01 00:00:00
abstract：:Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline o...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00093-8
更新日期：1998-08-01 00:00:00
abstract：:Trace amines are biological compounds that are still awaiting identification of their role in neuronal function. Using intracellular electrophysiological recordings, we investigated the depressant action of two trace amines (beta-phenylethylamine and tyramine) on the firing activity of dopaminergic neurons of the subs...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.11.031
更新日期：2004-05-01 00:00:00
abstract：:Increasing evidence suggests that oxidative stress may be implicated in the degeneration of dopaminergic neurons in Parkinson's disease (PD), and anti-oxidation have been shown to be effective to PD treatment. Myricetin has been reported to have the biological functions of anti-oxidation, anti-apoptosis, anti-inflamma...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.04.021
更新日期：2011-07-01 00:00:00
abstract：:The role of neurally born acetylcholine in the central modulation of cardiovascular short-term variability was assessed using a pharmacological probe physostigmine, a cholinesterase inhibitor that can act centrally also. Experiments were performed in instrumented conscious rats. Equidistant sampling at 20 Hz of systol...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.12.009
更新日期：2006-06-01 00:00:00
abstract：:There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the dist...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00155-7
更新日期：1996-01-01 00:00:00
abstract：:Alcohol damages the developing brain and can lead to fetal alcohol syndrome. One of alcohol's most important neuropathologic effects is neuronal death. As neurons mature, they become less vulnerable to alcohol-induced death because they acquire a protective signaling pathway, mediated by nitric oxide (NO). This pathwa...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.12.006
更新日期：2009-03-01 00:00:00
