Abstract:
:1. The role of oxidative stress, and accordingly uncontrolled reactive oxygen species generation/action, have been widely documented in a number of different neuronal pathologies. However, the concept of pharmacological interventions in prevention and therapy of oxidative stress-related diseases has not found adequate application in clinical practice. This may be due to the insufficient efficacy of drugs available, their unsuitable pharmacokinetics, side effects, toxicity, etc. 2. Based on stobadine, (--)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole, a well-known antioxidant, free radical scavenger, and neuroprotectant, it was attempted to develop new stobadine derivatives with improved pharmacodynamic and toxicity profiles, on applying molecular design, synthesis and adequate tests. Stobadine molecule was modified mostly by electron donating substitution on the benzene ring and by alkoxycarbonyl substitution at N-2 position. A total of >70 derivatives were prepared. 3. In a mice model of head trauma, some of the new stobadine derivatives administered i.v. immediately after the trauma, significantly improved sensomotoric outcome in the animals assessed 1 h later. Accordingly, decrease in brain edema was proved histologically as well as by brain wet weight assessment. 4. Putative neuroprotective action of the compounds was confirmed on rat hippocampal slices exposed to reversible 6 min hypoxia/low glucose by analysis of synaptic transmission in CA1 region neurons. Irreversible impairment of neurotransmission resulting from the hypoxia was significantly reduced by the presence of SMe1EC2, one of the new compounds, in concentration range 0.03-10.0x10(-6) mol l(-1). Both the neuroprotective and antioxidant effect of the compound closely resembled those of stobadine, melatonin, 21-aminosteroids, alpha-phenyl-tert-butylnitrone and others, all well-established antioxidants, except the range of effective concentrations was by 1-2 orders lower in SMe1EC2. 5. A remarkable antioxidant efficacy was observed in the new compounds in rat brain homogenates exposed to iron/ascorbate system by protection of lipids and creatine kinase against the oxidative impairment. A link between the neuroprotective and antioxidant/ scavenger properties in the compounds can be assumed. 6. Acute toxicity of some of the new pyridoindoles was diminished compared to stobadine. That might be due to the virtually full elimination of stobadine's undesired alpha (1)-adrenolytic activity attained by appropriate modifications of its molecule. 7. The new pyridoindoles extend the range of available neuroprotectants interfering with oxidative stress in neuronal tissue.
journal_name
Cell Mol Neurobioljournal_title
Cellular and molecular neurobiologyauthors
Stolc S,Snirc V,Májeková M,Gáspárová Z,Gajdosíková A,Stvrtina Sdoi
10.1007/s10571-006-9037-9subject
Has Abstractpub_date
2006-10-01 00:00:00pages
1495-504issue
7-8eissn
0272-4340issn
1573-6830journal_volume
26pub_type
杂志文章abstract::Neuroinflammation is an integral part of neurodegenerative diseases. Lipo-polysacharide (LPS) induces reactive astrogliosis, the cellular manifestation of neuroinflammation, in various models of neurological diseases, but its mechanism of action is still not properly known. The effect of guggulipid and nimesulide on L...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-011-9684-3
更新日期:2011-07-01 00:00:00
abstract::Hemorrhagic transformation (HT) is a common complication after thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in ischemic stroke. In this article, recent research progress of HT in vivo and in vitro studies was reviewed. We have discussed new potential mechanisms and possible experimental mode...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s10571-020-00985-1
更新日期:2020-10-30 00:00:00
abstract::Diabetic retinopathy (DR) is widely recognized as a neurovascular disease. Retina, being a neuronal tissue of the eye, produces neurotrophic factors for its maintenance. However, diabetes dysregulates their levels and thereby may damage the retina. Among neurotrophins, brain derived neurotrophic factor (BDNF) is the m...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-012-9901-8
更新日期:2013-04-01 00:00:00
abstract::Cell cultures are characterized by their simplicity, controllability, and ability to provide detailed basic information on how a particular cell population responds to specific stimuli or insult. These characteristics led to their extensive application in the study of molecular interactions and represent a valuable to...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-017-0483-3
更新日期:2017-11-01 00:00:00
abstract::1. An identified dopaminergic interneuron (RPeD1) of the snail Lymnaea stagnalis, makes specific synaptic connections with a number of target (VI and VJ) but not non-target (VF and RPB) neurons in vivo. When cultured in vitro with both target and non-target cells, RPeD1 re-establishes synapses with target cells only. ...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF02152058
更新日期:1996-10-01 00:00:00
abstract::1. Nitric oxide (NO) is thought to play a neuromodulatory role in the nervous system of vertebrate and invertebrate species. In the hornworm Manduca sexta, NO-mediated signaling has been implicated in behavioral and developmental processes, but its exact function in neurons is unknown. In this study, we identify speci...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-006-9091-3
更新日期:2007-03-01 00:00:00
abstract::Shen-Zhi-Ling (SZL) is a Chinese medicine formulated from a Kai-Xin-San decoction that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. However, the underlying mechanisms remain unclear. We investigated biological changes in depression patients (DPs) exhibiting antidepressant r...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10571-018-0582-9
更新日期:2018-07-01 00:00:00
abstract::1. Gamma-aminobutryic acid (GABA), a major inhibitory transmitter of the vertebrate retina, is synthesized from glutamate by L-glutamate decarboxylase (GAD) and mediates neuronal inhibition at GABAA receptors. GAD consists of two distinct molecular forms, GAD65 and GAD67, which have similar distribution patterns in th...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF00734812
更新日期:1991-10-01 00:00:00
abstract::The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (Aβ) peptides in brain, and immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were immunized with Aβ42 peptide was stopped when 6% of participants showed ...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-011-9680-7
更新日期:2011-08-01 00:00:00
abstract::The original version of this article unfortunately contained a typo in co-author name. ...
journal_title:Cellular and molecular neurobiology
pub_type: 已发布勘误
doi:10.1007/s10571-020-00990-4
更新日期:2020-10-31 00:00:00
abstract::The insulin-like growth factor (IGF) system is linked to CNS pathological states. The functions of IGFs are modulated by a family of binding proteins termed insulin-like growth factor binding proteins (IGFBPs). Here, we demonstrate that IGFBP-6 may be associated with neuronal apoptosis in the processes of intracerebra...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-016-0453-1
更新日期:2017-10-01 00:00:00
abstract::(1) There is increasing evidence that the cerebral endothelium and the blood-brain barrier (BBB) plays an important role in the oxidative stress-induced brain damage. The aim of the present study was to investigate the role of interendothelial junctional proteins in the BBB permeability increase induced by oxidative s...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-004-1378-7
更新日期:2005-02-01 00:00:00
abstract::1. Besides having a role in signal transduction, trimeric G proteins may also be involved in membrane trafficking events. In chromaffin cells, G alpha o has been found associated with the membrane of secretory granules. Here we examined the role of Go in regulated exocytosis using pressure microinjection combined with...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1023/a:1026329121099
更新日期:1997-02-01 00:00:00
abstract::1. Effects of 5-hydroxytryptamine (5-HT) on neuronal nicotinic acetylcholine (ACh) receptor channels were investigated by expressing cloned channel subunits in Xenopus oocytes. 2. When channels were expressed with a combination of alpha 3 and beta 4 subunits, 5-HT (10 to 300 microM) reversibly inhibited an inward curr...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF02071882
更新日期:1995-08-01 00:00:00
abstract::Abeta accumulation, a hallmark of Alzheimer's disease, promotes the disease progress in multiple facets. Abeta is formed through amyloidogenic cleavage pathway of amyloid precursor protein (APP). Production of Abeta can be decreased via activation of 5-HT2C receptor, which enhances alternative APP non-amyloidogenic cl...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-014-0138-6
更新日期:2015-04-01 00:00:00
abstract::The inhibitory effects of various opiates on developing rat vas deferens were studied by determining the degree of depression of mechanical responses elicited by electrical field stimulation. All agonists showed decreased effects with maturation, but the decrease occurred at different times. With normorphine the loss ...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF00716268
更新日期:1981-12-01 00:00:00
abstract::1. The retinoblastoma susceptibility gene product, p105Rb (RB), is an important regulator in the control of cell proliferation, differentiation, and apoptosis. Several cellular factors that complex with RB and exert their cellular regulatory functions have been identified, such as the RB:cyclophilin A (CypA) complex. ...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1023/b:cemn.0000005321.11544.cc
更新日期:2003-12-01 00:00:00
abstract::1. Angiotensin II receptors have been studied by quantitative autoradiography in selected brain areas of young (2-week-old) and adult (8-week-old) rats. 2. In young rats, angiotensin II receptors were present in brain areas which did not express receptors in the adult brain, such as thalamic nuclei, cortical areas, an...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF00769042
更新日期:1991-04-01 00:00:00
abstract::Exposing bovine chromaffin cells to a single 5 ns, high-voltage (5 MV/m) electric pulse stimulates Ca(2+) entry into the cells via L-type voltage-gated Ca(2+) channels (VGCC), resulting in the release of catecholamine. In this study, fluorescence imaging was used to monitor nanosecond pulse-induced effects on intracel...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-010-9573-1
更新日期:2010-11-01 00:00:00
abstract::Adeno-associated virus (AAV) has distinct advantages over other viral vectors in delivering genes of interest to the brain. AAV mainly transfects neurons, produces no toxicity or inflammatory responses, and yields long-term transgene expression. In this study, we first tested the hypothesis that AAV serotype 2 (AAV2) ...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-011-9674-5
更新日期:2011-08-01 00:00:00
abstract::The ataxia-telangiectasia mutated (ATM) protein is regarded as the linchpin of cellular defenses to stress. Deletion of ATM results in strong oxidative stress and degenerative diseases in the nervous system. However, the role of ATM in neuronal ischemic preconditioning and lethal ischemic injury is still largely unkno...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-019-00773-6
更新日期:2020-07-01 00:00:00
abstract::Besides clinical and imaging techniques, there is a lack of molecular makers for the diagnosis of Parkinson's disease (PD). There is an immense need to develop biomarkers associated with the phenotypes which may be valuable for individualized treatment. Single-nucleotide polymorphisms (PARK2: Ser167Asn (G>A) and Val38...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-019-00734-z
更新日期:2020-04-01 00:00:00
abstract::EP3 is prostaglandin E2 receptor subtype 3 and mediates the activation of several signaling pathways, changing in cAMP levels, calcium mobilization, and activation of phospholipase C. Previous studies demonstrated a direct role for EP3 in various neurodegenerative disorders, such as stroke and Alzheimer disease. Howev...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-015-0287-2
更新日期:2016-08-01 00:00:00
abstract::1. Oxytocin and vasopressin secretion from the neurohypophysis (NHP) is evoked by strongly patterned bursts of action potentials. We studied excitation-secretion coupling in single isolated terminals of rat NHP using patch clamp and capacitance detection techniques. 2. The secretory response evoked by trains of depola...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1023/a:1022575126738
更新日期:1998-02-01 00:00:00
abstract::To compare how different induction time takes effect on the proliferation and secretion ability of adipose-derived stem cell (ADSC)-induced Schwann-like cells (iSCs), ADSCs were isolated from healthy adult female rats. Flow cytometry (FCM) was performed to detect the ADSC-positive markers CD29, CD44, and CD90 and the ...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-020-00795-5
更新日期:2020-10-01 00:00:00
abstract::1. Synaptic vesicles (SVs) mediate fast regulated secretion of classical neurotransmitters. In order to perform their task SVs rely on a restrict set of membrane proteins. The mechanisms responsible for targeting these proteins to the SV membrane are still poorly understood. 2. Likewise, little is known about the intr...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1023/a:1021884319363
更新日期:2002-12-01 00:00:00
abstract::Organotellurium compounds have been synthesized since 1840, but pharmacological and toxicological studies about them are still incipient. Therefore, the objective of this study was to verify the effect of acute administration of the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of o...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-010-9547-3
更新日期:2010-10-01 00:00:00
abstract::(1) This study was to evaluate the anti-cholinesterase (ChE), cognition enhancing and neuroprotective effects of FS-0311, a bis-huperzine B derivative. (2) ChE activity was evaluated using a spectrophotometric method. Cognitive deficits in mice were induced by scopolamine or transient brain ischemia and reperfusion. W...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-007-9199-0
更新日期:2008-02-01 00:00:00
abstract::D-serine is synthesized by serine racemase (SR) and is a co-agonist at forebrain N-methyl-D-aspartate receptors (NMDARs). D-serine and SR are expressed primarily in neurons, but not in quiescent astrocytes. In this study, we examined the localization of D-serine and SR in the mouse striatum and the effects of genetica...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s10571-020-00880-9
更新日期:2020-05-22 00:00:00
abstract::1. Compared to pineal N-acetyl transferase (NAT) activity, which exhibited a dramatic drop following acute light exposure at night, nocturnal rat pineal thyroxine type II 5'-deiodinase (5'-D) activity was minimally influenced by the same light exposure. The injection of cycloheximide, a potent inhibitor of protein syn...
journal_title:Cellular and molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF00711228
更新日期:1988-12-01 00:00:00