Abstract:
:Cerebellar granule cells in culture develop survival requirements which can be met either by chronic membrane depolarization (25 mM K+) or by stimulation of ionotropic excitatory amino acid receptors. We observed previously that this trophic effect is mediated via Ca2+ influx, either through dihydropyridine-sensitive, voltage-dependent calcium channels (activated directly by high K+ or indirectly by kainate) or through N-methyl-D-aspartate receptor-linked ion channels. Steps after Ca2+ entry in the transduction cascade mediating the survival-supporting effect of high K+ and excitatory amino acids have now been examined. Using protein kinase inhibitors (H-7, polymixin B and gangliosides), and modulating protein kinase C activity by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, we obtained evidence against the involvement of protein kinase C and cyclic nucleotide-dependent protein kinases in the transduction cascade. On the other hand, calmidazolium (employed as a calmodulin inhibitor) counteracted the trophic effect of elevated K+ with high potency (IC50 0.3 microM), which exceeded by approximately 10-fold the potency for the blockade by the drug of voltage-sensitive calcium channels. The potency of calmidazolium in interfering with the N-methyl-D-aspartate rescue of cells was also much higher in comparison with the inhibition of 45Ca2+ influx through N-methyl-D-aspartate receptor-linked channels. Our results indicated that after calmodulin the next step in the trophic effects involves Ca2+/calmodulin-dependent protein kinase II activity. KN-62, a fairly specific antagonist of this enzyme, compromised elevated K+ or excitatory amino acid-supported cell survival with high potency (IC50 2.5 microM). In the relevant concentration range, KN-62 had little or no effect on Ca2+ entry through either voltage- or N-methyl-D-aspartate receptor-gated channels. Combining information on the toxic action of glutamate in "mature" granule cells with the trophic effect of either excitatory amino acids or high K+ treatment on "young" cells, we conclude that after the initial steps involving calcium in both cases the respective transduction pathways diverge. The toxic action of glutamate seems to be mediated through protein kinase C [Favaron et al. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 1983-1987 whereas a Ca2+/calmodulin-dependent protein kinase, which can be inhibited by KN-62 (but is resistant to gangliosides and to inhibitors whose potency is higher for protein kinase C than for Ca2+ calmodulin-dependent protein kinases, such as H-7 and polymixin B), is involved critically in the trophic effect.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Hack N,Hidaka H,Wakefield MJ,Balázs Rdoi
10.1016/0306-4522(93)90108-rsubject
Has Abstractpub_date
1993-11-01 00:00:00pages
9-20issue
1eissn
0306-4522issn
1873-7544pii
0306-4522(93)90108-Rjournal_volume
57pub_type
杂志文章相关文献
NEUROSCIENCE文献大全abstract::The action of mastoparan (a wasp venom peptide) on "maxi" Ca(2+)-activated K+ channels was studied in excised inside-out patch recordings from cultured bovine chromaffin cells, under normal conditions (160 mM K+ inside, 154 mM Na+ outside). Mastoparan, when applied on the intracellular side of the membrane reduced the...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(92)90456-c
更新日期:1992-10-01 00:00:00
abstract::The influence of transient increases in adrenal steroid hormones on the number of Fos-positive neurons after nociceptor activation was assessed in adrenalectomized rats. Fos protein, the product of the immediate early gene, c-fos, was detected immunocytochemically within the spinal trigeminal nucleus 2 h after noxious...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)00624-e
更新日期:1995-06-01 00:00:00
abstract::We have previously shown that the myristoylated alanine-rich C kinase substrate, a primary protein kinase C substrate in brain that binds and cross-links filamentous actin, is enriched in neuronal growth cones and is developmentally regulated in brain. Here we examined myristoylated alanine-rich C kinase substrate exp...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(00)00039-7
更新日期:2000-01-01 00:00:00
abstract::Electron probe X-ray microanalysis was used to measure water content and concentrations of elements (i.e. Na, K, Cl and Ca) in selected morphological compartments of rat optic nerve myelinated axons. Transaxolemmal movements of Na+ and Ca2+ were modified experimentally and corresponding effects on axon element and wat...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(97)00230-3
更新日期:1998-01-01 00:00:00
abstract::Correlated pre- and postsynaptic activity is thought to promote maturation of excitatory synapses in the developing brain by directing AMPA receptors to pure NMDA synapses. However, this hypothesis has not been tested in vivo. Here, we have performed such test by inhibiting correlated neural activity in vivo using a s...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(03)00366-x
更新日期:2003-01-01 00:00:00
abstract::Laminar organization is a fundamental cytoarchitecture in mammalian CNS and a striking feature of the neocortex. ER81, a transcription factor, has recently been utilized as a marker of cells in the layer 5 of the neocortex. We further pursued the distribution of ER81 to investigate the identity of the ER81-expressing ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2005.08.075
更新日期:2006-01-01 00:00:00
abstract::While B2 receptors mediate pain and hyperalgesia induced by bradykinin, in normal rats, recent reports indicate that, in the setting of inflammation, B1 receptors also mediate pain and hyperalgesia. Since bradykinin-induced hyperalgesia in normal rats is mediated by prostaglandins released from the postganglionic symp...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(95)00280-v
更新日期:1995-11-01 00:00:00
abstract::The distribution of gene expression domains during development constitutes a novel tool for the identification of distinct brain regions. This is particularly useful in the brain of amphibians where cell migration is very limited and most neurons organize in a periventricular layer. Here we report the expression patte...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(02)00326-3
更新日期:2002-01-01 00:00:00
abstract::The electrical activity of 132 neurons located in the inhibitory area of the medullary reticular formation, namely, in the medial aspects of the nucleus reticularis gigantocellularis, magnocellularis and ventralis has been recorded in precollicular decerebrate cats during sinusoidal displacement of the neck. This was ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(84)90038-1
更新日期:1984-02-01 00:00:00
abstract::The pontine projection of the flocculus and adjacent ventral paraflocculus was investigated with antegrade and retrograde axonal tracer techniques. Injections of horseradish peroxidase into the floccular complex revealed subsets of labeled neurons in the nucleus reticularis tegmenti pontis, the nucleus raphe pontis an...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(84)90049-6
更新日期:1984-03-01 00:00:00
abstract::The orexinergic neurons of the lateral hypothalamus (LH) are critical for wakefulness [McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302-330]. Recent evidence suggests that adenosine (AD), a homeostatic sleep factor, may act via A1 receptor (A1R) to control orexinergic activity and regulate sleep-...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.01.017
更新日期:2008-06-02 00:00:00
abstract::4-Aminopyridine (4-AP) is suggested to improve symptomatology of spinal injury patients because it may facilitate neuromuscular transmission, spinal impulse flow and the operation of the locomotor central pattern generator (CPG). Since 4-AP can also induce repetitive discharges from dorsal root afferents, this phenome...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2005.02.012
更新日期:2005-01-01 00:00:00
abstract::The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2017.07.064
更新日期:2017-11-19 00:00:00
abstract::Activation of the adenosine A(2A) receptor (A(2A)R) at the time of reperfusion has been shown to reduce ischemia-reperfusion injury in peripheral tissues and spinal cord. In this study we show that treating mice with the A(2A)R agonist, 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-pu...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2006.05.014
更新日期:2006-09-15 00:00:00
abstract::In an attempt to improve the survival of implanted dopamine cells, we have readdressed the optimal embryonic donor age for dopamine grafts. In a rat model of Parkinson's disease, animals with unilateral 6-hydroxydopamine lesions of the median forebrain bundle received dopamine-rich ventral mesencephalic grafts derived...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2007.03.037
更新日期:2007-06-08 00:00:00
abstract::Despite an abundance of studies on mechanisms of behavioral sensitization, considerable uncertainty exists as to whether alterations in dopamine neurotransmission underlie the exacerbated behavioral effects of cocaine observed during the early stages of abstinence. One of the factors contributing to the uncertainty an...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(02)00099-4
更新日期:2002-01-01 00:00:00
abstract::The protective effect of diphenyliodonium, known as an inhibitor of flavin enzymes including nitric oxide synthases, was examined against the neurotoxicity of excitatory amino acids on cultured spinal neurons of the rat. Diphenyliodonium reduced the neuronal damage induced by 15-min exposure to glutamate or N-methyl-D...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(96)00375-2
更新日期:1997-01-01 00:00:00
abstract::Acetylcholinesterase is released from both axon terminals and dendrites of nigrostriatal neurons. The relationship of this phenomenon to: (1) activation of receptors, and (2) firing rate, has been examined. In the first series of experiments, apomorphine or acetylcholine were infused into substantiae nigrae of urethan...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(86)90078-3
更新日期:1986-04-01 00:00:00
abstract::Previous studies have shown that when peripheral nerves in axolotl limbs are cut and surgically misdirected, regenerating axons grow back to the original pathways and innervate their correct muscles. In the present study however, we demonstrate that when given a choice between their correct nerve stump and an incorrec...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)00601-z
更新日期:1995-05-01 00:00:00
abstract::The acute behavioural and metabolic consequences of functional changes following unilateral intracaudate kainic acid at the level of the feline caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior were investigated. The present study became possible since it was previo...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(89)90240-6
更新日期:1989-01-01 00:00:00
abstract::Maternal separation (MS) during the first postnatal weeks induces alcohol intake and a reduction in the expression of glucocorticoid receptors (GR). Adults' alcohol consumption may depend on changes in the endocannabinoid system (eCBs). Our goal was to evaluate the status of the eCBs before the exposition to alcohol t...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2012.07.071
更新日期:2012-10-25 00:00:00
abstract::The effects of steady iontophoretic applications of serotonin on the spontaneous discharge and on the excitatory responses induced in deep cerebellar nuclei neurons by iontophoretic pulse applications of L-glutamate, L-aspartate, N-methyl-D,L-aspartate and quisqualate were studied in rat cerebellar slices maintained i...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(87)90072-8
更新日期:1987-11-01 00:00:00
abstract::Recent findings indicate that neurosteroids could act as important keys during the brain development. Fluctuations in neonatal allopregnanolone (AlloP) could result in altered pharmacological properties of the GABA(A) receptor system in adulthood. Recent studies demonstrated that neurosteroids play a critical role in ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.04.062
更新日期:2008-07-17 00:00:00
abstract::Hyperacusis, an exaggerated, sometimes painful perception of loudness even for soft sounds, is a poorly understood distressing condition. While the involvement of modified gain of central auditory neurons and the influence of nonauditory brain regions are well-documented, the issue of where in the auditory system thes...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2019.11.038
更新日期:2020-02-01 00:00:00
abstract::The present paper looks for kinematic similarities between whole-body and arm movements executed in the sagittal plane. Eight subjects performed sit-to-stand (STS) and back-to-sit (BTS) movements at their preferred speed in the sagittal plane. Kinematics analysis focused on shoulder motion revealed that STS was compos...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(02)00964-8
更新日期:2003-01-01 00:00:00
abstract::Pannexins (Panx) constitute a new family of gap junction type proteins. Functional expression in paired Xenopus oocytes indicated that pannexins are capable of forming communicating junctions but also proved to be active in forming of unopposed hemichannels. In the vertebrate brain pannexins have been found in neurons...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2007.01.061
更新日期:2007-04-25 00:00:00
abstract::Excitotoxic mechanisms involving alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)/kainate receptors play an important role in mediating cellular damage in spinal cord injury. However, the precise cellular mechanisms of glutamate release from non-synaptic white matter are not well understood. We examined ho...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(01)00385-2
更新日期:2001-01-01 00:00:00
abstract::Neuronal oscillations are important for information processing. The entorhinal cortex is one of the structures which is involved in generation of theta rhythm. The major role of the entorhinal cortex is to feed diverse sources of information both to and from the hippocampus. Far from simply being a funnel for this inf...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00113-4
更新日期:1998-08-01 00:00:00
abstract::Nitric oxide has been proposed to act as an intercellular messenger in central brainstem circuits controlling gastrointestinal motility. In particular, a subpopulation of preganglionic vagal neurons of the dorsal motor nucleus of the vagus have been shown to be reduced nicotinamide adenine dinucleotide phosphate(NADPH...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00586-7
更新日期:1999-05-01 00:00:00
abstract::Acute and chronic exposure to psychostimulants results in altered function of G-protein-coupled receptors in the forebrain. It is believed that neuroadaptations in G-protein signaling contribute to behavioral sensitivity to psychostimulants that persists over a prolonged drug-free period. Proteins termed activators of...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.03.013
更新日期:2010-06-16 00:00:00