Abstract:
:Increases in expression of α4βδ GABAA receptors (GABARs), triggered by fluctuations in the neurosteroid THP (3α-OH-5α[β]-pregnan-20-one), are associated with changes in mood and cognition. We tested whether α4βδ trafficking and surface expression would be altered by in vitro exposure to flumazenil, a benzodiazepine ligand which reduces α4βδ expression in vivo. We first determined that flumazenil (100 nM-100 μM, IC50=∼1 μM) acted as a negative modulator, reducing GABA (10 μM)-gated current in the presence of 100 nM THP (to increase receptor efficacy), assessed with whole cell patch clamp recordings of recombinant α4β2δ expressed in HEK-293 cells. Surface expression of recombinant α4β2δ receptors was detected using a 3XFLAG reporter at the C-terminus of α4 (α4F) using confocal immunocytochemical techniques following 48 h exposure of cells to GABA (10 μM)+THP (100 nM). Flumazenil (10 μM) decreased surface expression of α4F by ∼60%, while increasing its intracellular accumulation, after 48 h. Reduced surface expression of α4β2δ after flumazenil treatment was confirmed by decreases in the current responses to 100 nM of the GABA agonist gaboxadol. Flumazenil-induced decreases in surface expression of α4β2δ were prevented by the dynamin blocker, dynasore, and by leupeptin, which blocks lysosomal enzymes, suggesting that flumazenil is acting to increase endocytosis and lysosomal degradation of the receptor. Flumazenil increased the rate of receptor removal from the cell surface by 2-fold, assessed using botulinum toxin B to block insertion of new receptors. These findings may suggest new therapeutic strategies for regulation of α4β2δ expression using flumazenil.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
Kuver A,Smith SSdoi
10.1016/j.brainresbull.2015.11.015subject
Has Abstractpub_date
2016-01-01 00:00:00pages
131-43eissn
0361-9230issn
1873-2747pii
S0361-9230(15)30066-6journal_volume
120pub_type
杂志文章abstract::This paper reviews and provides new data on the relationship of the peptide content in rat dorsal root ganglion (DRG) neurons to a) the neurofilament content of the soma and b) the conduction velocities of the fibres. The latter involved intracellular recordings made in vitro followed by dye injection and immunocytoch...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(93)90250-f
更新日期:1993-01-01 00:00:00
abstract::We examined whether reticulospinal sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) have muscarinic receptors and ACh inputs, and whether these cholinergic mechanisms on RVLM neurons are involved in the pressor response induced by peripheral administration of physostigmine. Microiontophoretic app...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(96)00256-0
更新日期:1997-01-01 00:00:00
abstract::Small GTPases of the rho family regulate the extensive rearrangements of the cytoskeleton that characterize neuronal differentiation. Citron kinase is a target molecule for activated rhoA, previously implicated in control of cytokinesis. We have found that, in addition, it could play an important role in modulating th...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(03)00058-3
更新日期:2003-05-30 00:00:00
abstract::The developmental neurotoxicity of organophosphate pesticides targets serotonin (5HT) systems, which are involved in emotional and appetitive behaviors. We exposed neonatal rats to daily doses of diazinon on postnatal days 1-4, using doses (0.5 or 2mg/kg) spanning the threshold for barely-detectable cholinesterase inh...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2007.10.008
更新日期:2008-03-28 00:00:00
abstract::Ongoing maternal behavior in rats is under the inhibitory influence of opiates. Exposure to drugs of abuse may result in a progressive and enduring enhancement of their reinforcing effects. Little attention has been paid to the possibility that puerperal treatment with morphine may lead to sensitization to this drug, ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(01)00549-4
更新日期:2001-07-01 00:00:00
abstract::This investigation assessed the relative reliability of the human auditory evoked potential (AEP) amplitude-intensity and latency-intensity functions. Averaged AEP waveforms to 10 levels of stimulus magnitude were obtained from bipolar recordings. Variability and slope of group functions were constant, as indicated by...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(80)90195-1
更新日期:1980-03-01 00:00:00
abstract::Hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine (NIC) are sexually diergic: Female rats have higher adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than do males. In the present study we determined HPA responses in male and female rats following single doses of NIC, a sing...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2011.03.001
更新日期:2011-05-30 00:00:00
abstract::The most severe manifestation of Herpes Simplex Type 1 virus (HSV-1) infection is encephalitis characterized by arousal impairment and seizures that can evolve to coma and death. Previous studies reported the involvement of suppressor of cytokine signaling (SOCS) proteins, specifically SOCS1 and SOCS3, in HSV-1 infect...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2016.09.011
更新日期:2016-10-01 00:00:00
abstract::We quantitated the activity of ornithine decarboxylase (ODC) in homogenates and subcellular fractions of inner ear tissues from the rat and guinea pig and demonstrate inhibition of cochlear ODC by the aminoglycoside neomycin. Subcellular fractionation showed the enzyme associated with the post-mitochondrial supernatan...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(87)90056-6
更新日期:1987-12-01 00:00:00
abstract::An improved comparative interpretation of the teleostean forebrain suggests that the dorsal tier (Vd,Vc) and ventral tier (Vv,Vl) nuclei of the ventral telencephalic area (subpallium) represent the striatum and septum, respectively. Among other arguments, a dopaminergic innervation originating in the diencephalic post...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/s0361-9230(01)00666-9
更新日期:2002-02-01 00:00:00
abstract::The effect of lithium chloride on the activity of the afferent nerve fibers from the abdominal organs was studied in anesthetized rats. The administration of the lithium chloride solution (0.15 M) over the mesentery increased afferent discharge rate of the splanchnic and vagal gastric nerve. Injection of the same solu...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(94)90094-9
更新日期:1994-01-01 00:00:00
abstract::Chronic brain implants are accompanied by a tissue response that causes the loss of neurons in the vicinity of the implant and the formation of a glial scar that is also referred to as foreign body response. Despite immense progress in the field of brain-computer interface (BCI) research the biocompatibility of chroni...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2015.08.001
更新日期:2015-08-01 00:00:00
abstract::Functional interactions between the basal ganglia and the perioral area were analyzed by means of electrical brain stimulation in the rat. The first experiment showed that unilateral stimulation of the substantia nigra sensitized the contralateral perioral area for a biting reflex upon its tactile stimulation. This bi...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(91)90241-b
更新日期:1991-02-01 00:00:00
abstract::Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of o...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2018.08.008
更新日期:2018-09-01 00:00:00
abstract::Preprodynorphin and preproenkephalin are protein precursors from which are derived two classes of opioid neurotransmitter peptides. Dynorphin A((1-17)) is produced by proteolytic processing of prodynorphin, and processing of proenkephalin yields the enkephalin peptides. We report here on the isolation and sequencing o...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2004.01.008
更新日期:2004-03-15 00:00:00
abstract::Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, a...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2006.08.004
更新日期:2006-12-11 00:00:00
abstract::Alzheimer's disease (AD) is a worldwide progressive neurodegenerative disorder in the elderly. Previous research has indicated that Alzheimer's disease impairs white matter (WM) tracts. Anatomical and neuroimaging studies have indicated that WM tracts are associated with cognitive function. Whether the abnormal WM int...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2018.09.010
更新日期:2018-10-01 00:00:00
abstract::The olfactory bulbectomized (OBX) rat model of depression has been widely used in studies on the behavioral and neurochemical aspects of human depression. The objective of the present investigation was to assess open field (OF) activity and the brain regional 5-HT(1A) receptor densities of the sham operated (SHX) and ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2007.09.005
更新日期:2008-03-28 00:00:00
abstract::A number of biological risk factors have been implicated for Alzheimer's disease (AD). The investigation of prevalence rates of AD in crosscultural populations has much potential in validating these factors. We previously assessed brain amyloid beta (A beta) protein deposition and other lesions associated with AD as p...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/s0361-9230(97)00310-9
更新日期:1997-01-01 00:00:00
abstract::Three sets of experiments have been conducted that suggest that adrenal glucocorticoids play a role in the long-term control of intake and in dietary preferences. First, obesity is dependent upon glucocorticoid-modulated metabolic pathways. Surgical or pharmacological manipulations in obese animals that eliminate or d...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(91)90136-8
更新日期:1991-09-01 00:00:00
abstract::Axons of retinal ganglion cells showed responses not previously emphasized: (a) many tonic units discharged oscillations, 2--12 spikes per burst, interburst intervals 20--300 msec; (b) phasic units showed concentric or flanking ON and OFF fields, response frequency depended on balance of retinal excitation and inhibit...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(76)90080-0
更新日期:1976-11-01 00:00:00
abstract::In accordance with the genetic nature of Huntington's disease (HD), transgenic and knock-in mouse models have been developed that have sought to recapitulate the key features of the human condition. To date, only a single rat model has been developed, the tgHD rat that carries 51 CAG repeats. The tgHD rat has many of ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2009.03.003
更新日期:2009-06-30 00:00:00
abstract::Crested Ducks (CR) occasionally show intracranial fat bodies. Additionally, behavioral abnormalities such as motor incoordination can be observed. Here, it is shown that a behavioral test helps to identify CR that have a problematical fat body. The ducks were put on their backs, and the time required for them to stand...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2008.03.009
更新日期:2008-06-15 00:00:00
abstract:OBJECTIVE:Transcranial near-infrared stimulation (tNIRS) can penetrate the scalp and skull and can reach the superficial layers of the cerebral cortex. In this study, we evaluated whether an 820-nm tNIRS can modulate the excitability of the primary motor cortex (M1) as measured by transcranial magnetic stimulation (TMS...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2019.12.007
更新日期:2020-02-01 00:00:00
abstract::This study was performed to elucidate the mechanism by which adenosine triphosphate (ATP) encapsulated into liposomes was able to protect against experimental brain ischemia in the rat. After intracarotidal administration of liposomally entrapped ATP, the ATP blood level increased dramatically whereas no change was ob...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(91)90004-4
更新日期:1991-03-01 00:00:00
abstract::The present study was conducted to examine the effects of d-amphetamine and the designer drugs 3,4-methylenedioxymethamphetamine (MDMA), N-methyl-3,4-methylenedioxyphenyl-3-butamine (HMDMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-1-ethanamine (MDM1EA) in the chick embryo and the young ch...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(94)90011-6
更新日期:1994-01-01 00:00:00
abstract::Serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) are key modulators of molecular signaling, cognition and behavior. Although SERT and BDNF mutant mouse phenotypes have been extensively characterized, little is known about their self-grooming behavior. Grooming represents an important behaviora...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2012.08.004
更新日期:2012-12-01 00:00:00
abstract::Transcription factor Pbx4 is recruited to form dimeric or trimeric complexes with Hox and/or Meis homeodomain proteins and participates in patterning the hindbrain and retina during vertebrate CNS development. We characterized a Pbx4 cDNA isolated from a Gekko japonicus brain and spinal cord cDNA library. Northern blo...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2009.08.010
更新日期:2009-12-16 00:00:00
abstract::The failure of regenerating axons to grow within the adult mammalian central nervous system (CNS) does not apply to the olfactory bulb (OB). In this structure, normal and transected olfactory axons are able to enter, regenerate, and reestablish lost synaptic contacts with their targets, throughout the lifetime of the ...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/s0361-9230(97)00463-2
更新日期:1998-06-01 00:00:00
abstract::The involvement of alpha-amino-3-hydroxy-5-methylizoxazole-4-propionic acid (AMPA) receptors in induction of long-term potentiation (LTP) was examined in rat hippocampal slice preparation. Using conventional extracellular recording, excitatory postsynaptic potentials (EPSPs) and population action potentials (PSs), evo...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(00)00288-4
更新日期:2000-08-01 00:00:00