Abstract:
:We have previously shown that the HSV-2 anti-apoptotic protein ICP10PK is delivered by the replication incompetent virus mutant DeltaRR and prevents kainic acid (KA)-induced epileptiform seizures and neuronal cell loss in the mouse and rat models of temporal lobe epilepsy. The present studies used DeltaRR and the ICP10PK deleted virus mutant DeltaPK to examine the mechanism of neuroprotection. DeltaRR-infected neuronal cells expressed a chimeric protein in which ICP10PK is fused in frame to LacZ (p175) while retaining ICP10PK kinase activity. DeltaPK-infected neuronal cells expressed a mutant ICP10 protein that is deleted in the PK domain and is kinase negative (p95). p175 and p95 were expressed in CA3 (86+/-3%) and CA1 (69+/-7%) cells from DeltaRR or DeltaPK-infected organotypic hippocampal cultures (OHC) and 80-85% of the ICP10 positive cells co-stained with antibody to beta(III) Tubulin (neuronal marker). DeltaRR, but not DeltaPK, inhibited KA-induced cell death and caspase-3 activation in CA3 neurons, an inhibition seen whether DeltaRR was delivered 2 days before or 2 days after KA administration (95% neuroprotection). Neuroprotection was associated with ERK and Akt activation and was abrogated by simultaneous treatment with the MEK (U0126) and PI3-K (LY294002) inhibitors. DeltaRR-mediated neuroprotection was associated with increased expression of the anti-apoptotic protein Bag-1 and decreased expression of the pro-apoptotic protein Bad. The surviving neurons retained normal synaptic function potentially related to increased expression of the transcription factor CREB. The data indicate that DeltaRR is a promising platform for neuroprotection from excitotoxic injury.
journal_name
Brain Resjournal_title
Brain researchauthors
Gober MD,Laing JM,Thompson SM,Aurelian Ldoi
10.1016/j.brainres.2006.08.078subject
Has Abstractpub_date
2006-11-13 00:00:00pages
26-39issue
1eissn
0006-8993issn
1872-6240pii
S0006-8993(06)02436-Xjournal_volume
1119pub_type
杂志文章相关文献
BRAIN RESEARCH文献大全abstract::The present experiments describe the effect of NMDA and kainate agonists of the NMDA and non-NMDA subtype of receptors respectively of the excitatory amino acids (EAAs) system in prepubertal (16 days of age) and peripubertal (30-day-old rats) male rats on the in vitro hypothalamic release of GnRH, and on the in vivo L...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(95)01216-8
更新日期:1996-01-29 00:00:00
abstract::A normobar hypoxia (9% oxygen) of 8 h reduces the neurotoxicity of a subcutaneous injection of 10 mg/kg kainic acid given one week later. Both seizures and degenerative changes, including cell death of hippocampal and cortical neurons are markedly decreased by hypoxia. It is also shown that hypoxia also markedly reduc...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(94)91693-4
更新日期:1994-05-02 00:00:00
abstract::After the microinjection of morphine (5 micrograms/0.5 microliter) into the periaqueductal gray resulted in an increase in the hot-plate and tail-flick response latency of the unanesthetized rat, the alpha-adrenergic antagonists yohimbine, rauwolscine and corynanthine were given intrathecally. This treatment resulted ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(85)90424-x
更新日期:1985-06-10 00:00:00
abstract::To gain greater insight on the molecular mechanisms that underlie ischemic stroke, we compared gene expression profiles in transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) stroke models using Expression Analysis Systematic Explorer (EASE) pathway analysis software. Many transcripts were induced...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2005.11.090
更新日期:2006-02-03 00:00:00
abstract::A differential role has been suggested for two important areas in the neural circuitry of stress, central nucleus of the amygdala (CeA) and bed nucleus of stria terminalis (BNST) in the extended amygdala, in regulating fear versus anxiety. Since chronic stress enhances anxiety and consolidation of aversive memories, w...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(02)04162-8
更新日期:2003-03-07 00:00:00
abstract::Recent studies, which have shown an increase of plasma vasopressin (VP) in experimental motion sickness and the efficacy of VP antagonists for motion sickness, suggest an important role of VP in the development of vestibulo-autonomic responses. We have recently found evidence of the co-existence of vasopressinergic ne...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(01)02799-8
更新日期:2001-09-28 00:00:00
abstract::The reactivity of dopaminergic (DA) terminals in the nucleus accumbens was investigated in male rats submitted to tail-pinch or various social interactions. The DA activity was assessed by measurement of the presynaptic metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) by using differential pulse voltammetry in free m...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(86)90646-3
更新日期:1986-11-12 00:00:00
abstract::Spreading depression (SD) is a wave of cellular depolarization which contributes to neuronal damage in experimental focal ischaemia, and may also underlie the migraine aura. The purpose of this study was to examine the effects of probenecid, an inhibitor of organic anion transport, on K+-evoked SD in vivo. Microdialys...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(97)00434-4
更新日期:1997-08-01 00:00:00
abstract::Seventy-two hybridoma lines that produce monoclonal antibodies to molecules of a rat synaptosomal plasma membrane fraction (SPM) were generated. The topographical distribution of the antigens in the cerebellum and other areas of the brain was studied by light microscopy immunocytochemistry. Some of the antibodies reco...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(84)90118-5
更新日期:1984-11-26 00:00:00
abstract::Daily changes in tryptophan-5-hydroxylase (TrH) activity have been studied in six different 5-HT-containing cell groups (B3, B4, B5, B6, B7, B8,) in the brain stem of rats maintained in a regular cycle of 12 h of light and 12 h of darkness. Significant circadian alternations of TrH activity were observed in most of th...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(77)90647-3
更新日期:1977-03-04 00:00:00
abstract::gamma-Aminobutyric acid (GABA) receptor was solubilized from synaptic membrane of the rat brain by various detergents. Nonidet P-40, a non-ionic detergent, was found to be an effective solubilizing agent, since it caused no interference on the receptor binding assay, yielded a [3H]muscimol binding protein with a high ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(82)90720-x
更新日期:1982-03-25 00:00:00
abstract::The purpose of this study was to compare the relative effects of mannitol and hypertonic saline (HTS) on calpain activity, apoptosis and neuroinflammatory response induced by experimental cortical contusion. Four groups of 5 Sprague-Dawley male rats were submitted to focal brain injury produced by exposing the parieta...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2006.05.045
更新日期:2006-07-26 00:00:00
abstract::To determine the contribution by mast cells to the brain content of histamine (HA) and its metabolite tele-methylhistamine (t-MH), the number of mast cells, as well as the levels of HA and t-MH were measured in brain regions of mast cell-deficient (W/Wv) and control (+/+) mice. In agreement with earlier studies, mast ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(84)90897-7
更新日期:1984-01-30 00:00:00
abstract::The organization of corticotectal projections from the medial agranular cortex (AGm), which has been considered to contain rat's frontal eye field, was examined using anterograde and retrograde tracing techniques. When biotinylated dextranamine (BDA) injections were made into the rostral part of the AGm, small numbers...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(01)02437-4
更新日期:2001-06-08 00:00:00
abstract::This study shows that the axons of some raphespinal sympathoinhibitory neurons projecting to the third thoracic spinal segment emit branches in the third-fourth cervical spinal segments of cats. This was demonstrated by using time-controlled collision of neuronal action potentials initiated by stimuli applied at these...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(88)91417-5
更新日期:1988-02-16 00:00:00
abstract::The primary objective of this study was to test the hypothesis that intravenous administration of autologous bone marrow cells could improve functional recovery after middle cerebral artery occlusion (MCAO) for 45 min in the rat and to determine specific time windows for efficacy. Mononuclear cells from autologous bon...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2003.09.084
更新日期:2004-05-08 00:00:00
abstract::Since several different pathways are involved in cerebral ischemia/reperfusion injury, combination therapy rather than monotherapy may be required for efficient neuroprotection. In this study, we examined the protective effects of an apoptosis inhibitor Gly(14)-humanin (HNG) and a necroptosis inhibitor necrostatin-1 (...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2010.07.080
更新日期:2010-10-08 00:00:00
abstract::Intracellular recordings were obtained from facial motoneurons in anesthetized rats. The effects of iontophoretically applied serotonin were compared to those of the excitatory amino acids glutamate and DL-homocysteic acid (DLH), and the inhibitory amino acids, glycine, GABA and muscimol, under various conditions of m...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(82)90838-1
更新日期:1982-05-06 00:00:00
abstract::The behaviour and cognitive abilities of marmosets with bilateral ablations of either the archicortex on the mediodorsal surface or the paleocortex on the ventrolateral surface of the frontal lobes were assessed in terms of the types of information being handled, the mode of action (inhibitory versus productive mechan...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(93)90937-i
更新日期:1993-11-19 00:00:00
abstract:BACKGROUND:Previous studies have shown that regulating the target region by real-time fMRI-based neurofeedback training can influence the activation of other regions and the functional connectivity between them. However, it is not clear whether the training effect of neurofeedback, especially in emotion regulation, is ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2020.146853
更新日期:2020-08-01 00:00:00
abstract::Monkeys were trained to depress a hold key for a period of 2 sec. After this hold period, either a red or a green cue lamp appeared in random sequence. The red lamp required the monkey to move his hand from the hold key to a target button within 1 sec of the cue presentation. The green lamp required continued depressi...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(76)90986-0
更新日期:1976-01-09 00:00:00
abstract::Serial ion-exchange and high-performance liquid chromatography separations were employed for the tissue extraction and purification of kynurenic acid (KYNA). Subsequently, the compound isolated from postmortem human brain tissue was unequivocally identified as KYNA by nuclear magnetic resonance and mass spectrometric ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(88)90815-3
更新日期:1988-06-28 00:00:00
abstract::Serotonin (5HT) is thought to reset the biological clock in the suprachiasmatic nuclei (SCN) in vitro through a postsynaptic 5HT-1a receptor. Thus we examined 5HT receptor gene expression in the SCN by in situ hybridization. On film autoradiograms, 5HT-1c receptor mRNA showed intense SCN hybridization, while 5HT-1b re...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(93)90789-p
更新日期:1993-04-09 00:00:00
abstract::In this study, a single unit activity was recorded in the nucleus paragigantocellularis (PGi), located in the rostral ventrolateral medulla of anesthetized, morphine-dependent rats. The spontaneous activity of PGi neurons was significantly decreased by administration of morphine (10 mg/kg; i.p.) in sham-operated, cont...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(98)01029-4
更新日期:1998-12-14 00:00:00
abstract::The pathogenic mechanisms of gene-environment interactions determining variability of human neurodevelopmental disorders remain unclear. In the two consecutive papers, we used the neonatal Borna disease virus (BDV) infection rat model of neurodevelopmental damage to evaluate brain pathology, monoamine alterations, beh...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(02)02723-3
更新日期:2002-07-19 00:00:00
abstract::Knife cuts in the frontal plane separating the anterior part of the caudate-putamen from the globus pallidus resulted in marked decreases in substances P levels in the reticular part of the substantia nigra. More caudal knife cuts were required in order to effect maximal decreases in nigral glutamic acid decarboxylase...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(77)91034-4
更新日期:1977-10-28 00:00:00
abstract::In this study we compare the distribution of the phosphoprotein B-50 in two regions of immature and adult rat brain using affinity-purified antibodies to B-50. In the cerebellum of the 8-day-old rat we observed distinct patterns of distribution of B-50 immunoreactivity (BIR) in the premigratory zone and the developing...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(86)90747-x
更新日期:1986-06-11 00:00:00
abstract::In a previous study we reported significant elevations of TRH in neocortex, hippocampus and combined amygdala/pyriform cortex in rats 48 h after the last of a series of stage 5 kindled seizures. In the present study, to determine whether the increases in TRH were proportional to the intensity of the convulsions, and t...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(90)91330-j
更新日期:1990-08-13 00:00:00
abstract::Manipulations of either discrete emotions (e.g. happiness) or affective dimensions (e.g. positivity) have a long tradition in emotion research, but interactive effects have never been studied, based on the assumption that the two underlying theories are incompatible. Recent theorizing suggests, however, that the human...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2014.03.045
更新日期:2014-05-20 00:00:00
abstract::A major function of the dopamine in the striatum is to control the activity of its efferent systems which contain primarily GABAergic neurons. Direct intracerebral injections of haloperidol into the corpus striatum impaired the performance of rats trained to depress a lever in a sensitive reaction time task. Rats were...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(89)90186-8
更新日期:1989-04-03 00:00:00