Abstract:
:Apoptosis is a form of cell death historically defined by morphological and biochemical changes that occur in the cell body and nucleus. However, in contrast to nonneuronal cells in which apoptosis has been most intensively studied, neurons exhibit elaborate morphologies with synaptic connections often located at sites a great distance from the cell body. Signaling events occurring in synaptic terminals are believed to play important roles in either promoting (e.g., activation of glutamate receptors in postsynaptic spines) or preventing (e.g., activation of neurotrophic factors in presynaptic terminals) neuronal cell death in various physiological and pathological settings. We have found that apoptotic biochemical cascades can be activated locally in synaptic terminals and neurites and have shown that such cascades can result in local functional and morphological alterations and can also propagate to the cell body resulting in neuronal death. Prostate apoptosis response-4 production, caspase activation, loss of plasma membrane phospholipid asymmetry, mitochondrial dysfunction, and production of factors capable of inducing nuclear chromatin condensation and fragmentation can all occur locally in synaptic terminals in response to various stimuli. Activation of receptors for neurotrophic factors (e.g., basic fibroblast growth factor, secreted form of amyloid precursor protein alpha, and activity-dependent neurotrophic factor) and cytokines (e.g., tumor necrosis factor-alpha) in synaptic terminals can exert synaptoprotective actions that either can be transduced locally or may require signals to the nucleus and back. In addition to their roles in synaptic degeneration and neuron death, apoptotic cascades may play roles in synaptic plasticity. For example, we found that caspase activation can lead to proteolysis of certain glutamate receptor subunits and that this action of capases is correlated with reduced calcium responses to glutamate. We propose that apoptotic cascades function in a continuum in which low levels of activation play roles in adaptive responses to "stressors," whereas higher levels of activation mediate synaptic degeneration and cell death.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Mattson MP,Duan Wkeywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
152-66issue
1eissn
0360-4012issn
1097-4547pii
10.1002/(SICI)1097-4547(19991001)58:1<152::AID-JNRjournal_volume
58pub_type
杂志文章,评审abstract::Traumatic brain injuries (TBIs) pose a massive burden of disease and continue to be a leading cause of morbidity and mortality throughout the world. A major obstacle in developing effective treatments is the lack of comprehensive understanding of the underlying mechanisms that mediate tissue damage and recovery after ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.24054
更新日期:2018-04-01 00:00:00
abstract::In recent years, several novel types of disorders have been characterized, including what have been termed polyalanine diseases, in which patients have expanded triplet repeats in specific genes, resulting in the translation of aberrantly elongated polyalanine stretches. In this study, we showed that yellow fluorescen...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.21619
更新日期:2008-05-15 00:00:00
abstract::We studied the effects of oxygen-derived free radicals on the ultrastructure of brain cortical slices and the release of fatty acids from phospholipids of crude synaptosomes. Xanthine oxidase, hypoxanthine, and ADP-Fe3+, a free-radical-generating system, caused swelling of cellular processes and mitochondria. The oxyg...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490120408
更新日期:1984-01-01 00:00:00
abstract::We have recently demonstrated that brain plastic events significantly modify synaptic protein synthesis measured by the incorporation of [(35)S]methionine in brain synaptosomal proteins. Notably, in rats learning a two-way active avoidance task, the local synthesis of two synaptic proteins was selectively enhanced. Be...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.22037
更新日期:2009-07-01 00:00:00
abstract::Small-diameter myelinated CNS axons are preferentially affected in multiple sclerosis (MS) and in the hereditary spastic paraplegias (HSP), in which the distal axon degenerates. Mitochondrial dysfunction has been implicated in the pathogenesis of these and other disorders involving axonal degeneration. The aim of this...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.21672
更新日期:2008-08-01 00:00:00
abstract::Quercetin, a strong free radical scavenger, is investigated for neuroprotective effects in a Neuro 2a cell line conditionally transfected with 16Q huntingtin (Htt) and 150Q Htt, which express the protein upon stimulation. Cells were protected from death by a 20-µM dose of quercetin on the second day of Htt induction, ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.23618
更新日期:2015-10-01 00:00:00
abstract::gamma-Aminobutyric acid (GABA) regulates the proliferation and migration of olfactory bulb (OB) interneuron progenitors derived from the subventricular zone (SVZ), but the role of GABA in the differentiation of these progenitors has been largely unexplored. This study examines the role of GABA in the differentiation o...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.22055
更新日期:2009-08-01 00:00:00
abstract::Noise exposure is one of the most common causes of hearing loss. Recent studies found that noise exposure-induced cochlear damage may change the excitability and tonotopic organization of the central auditory system (CAS). This plasticity was suspected to be related to tinnitus and hyperacusis. However, how cochlear d...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.23152
更新日期:2013-02-01 00:00:00
abstract::By using two different approaches, ubiquitin C-terminal hydrolase 1 (UCHL1) was identified as a potential cerebrospinal fluid (CSF) biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage (ASAH) and presumably other CNS damage and disease states. Appropriate antibodies and a sensitive ELISA were generated, an...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.22323
更新日期:2010-05-15 00:00:00
abstract::The higher prevalence and risk for Alzheimer's disease in women relative to men has been partially attributed to the precipitous decline in gonadal hormone levels that occurs in women following the menopause. Although considerable attention has been focused on the consequence of estrogen loss, and thus estrogen's neur...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.21370
更新日期:2007-08-15 00:00:00
abstract::The interaction of bovine white matter proteolipid apoproteins with sodium dodecyl sulfate (SDS) was studied. Equilibrium dialysis binding measurements show that the apoprotein binds approximately 1.5 gm SDS per gram protein at high ionic strength (gamma/2 = 0.17). At low ionic strength (gamma/2 = 0.01) the protein bi...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490060602
更新日期:1981-01-01 00:00:00
abstract::The mast cell, an immunocompetent cell that contributes to neurogenic inflammation in a variety of tissues, including synovium, is found in close proximity to peripheral terminals of unmyelinated primary afferents and sympathetic postganglionic nerve terminals. In this study we evaluated the hypothesis that the densit...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490260306
更新日期:1990-07-01 00:00:00
abstract::A series of AMPA [(R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid] analogues were evaluated for activity at homomeric, heteromeric, and chimeric rat GluR1(o) and GluR3(o) receptors expressed in Xenopus oocytes, using the two-electrode voltage clamp technique. The formation of heteromeric receptor compl...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(sici)1097-4547(19970715)49:2<176::aid-jnr
更新日期:1997-07-15 00:00:00
abstract::In contrast to mammals, teleost fish are able to regrow severed long-range projection axons in the central nervous system (CNS), leading to recovery of function. The optic projection in teleost fish is used to study neuron-intrinsic and environmental molecular factors that determine successful axon regrowth and naviga...
journal_title:Journal of neuroscience research
pub_type: 杂志文章,评审
doi:10.1002/jnr.21121
更新日期:2007-09-01 00:00:00
abstract::Embryonic central nervous system neuroepithelial cells are a transient population of cells that give rise to neuronal and glial progenitors. In the E12-E16 embryonic rat spinal neural tube we have identified neuroepithelial cells as radially oriented cells expressing the GD3 ganglioside as recognized by the monoclonal...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4547(19960901)45:5<549::AID-JNR
更新日期:1996-09-01 00:00:00
abstract::HEPES inhibited the taurine uptake in glial cells. A different kind of inhibition was observed when HEPES was present in the culture medium or in the incubation medium used for the taurine-uptake measurement. As an example of a possible interference of HEPES in pharmacological experiments, we have studied the effect o...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490230111
更新日期:1989-05-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has been implicated in the pathogenesis of several disorders and injuries in the central nervous system (CNS). Unlike IGF-I, which promotes CNS growth, TNF-alpha causes brain growth retardation and neural damage. Recently TNF-alpha has been shown to ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.10512
更新日期:2003-03-01 00:00:00
abstract::The mechanisms underlying brain seizure tolerance, a phenomenon in which brief periods of seizures protect brain against the lethal effects of subsequent sustained seizures, are poorly understood. Because brain seizure tolerance and brain ischemia tolerance likely share certain common mechanisms, the recent evidence t...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20566
更新日期:2005-08-15 00:00:00
abstract::In the non-amyloidogenic pathway, the Alzheimer's amyloid precursor protein (APP) is cleaved within the amyloid-beta domain by alpha-secretase precluding deposition of intact amyloid-beta peptide. The large ectodomain released from the cell surface by the action of alpha-secretase has several neuroprotective propertie...
journal_title:Journal of neuroscience research
pub_type: 杂志文章,评审
doi:10.1002/jnr.10737
更新日期:2003-11-01 00:00:00
abstract::Motoneuron number and expression of cytoplasmic RNA and ribosomal RNA (rRNA) gene transcription activity in the facial nucleus were examined quantitatively and chronologically for up to 4 weeks in rats after facial nerve axotomy and avulsion in order to elucidate interrelationships in axonal changes. The right facial ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.21495
更新日期:2008-02-01 00:00:00
abstract::Cultured purified oligodendroglia and astroglia exposed to heat stress (45 degrees C, 10 or 20 min) synthesized a 68-kDa heat-stress protein, which migrates on two-dimensional gel electrophoresis and reacts with a specific monoclonal antibody suggesting it is similar to a major 72-kDa heat-shock protein previously rep...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490200103
更新日期:1988-05-01 00:00:00
abstract::Alpha2-adrenergic receptors control norepinephrine (NE) release and tumor necrosis factor-alpha (TNF) production from neurons. TNF regulates NE release, depending on alpha2-adrenergic receptor functioning. The relationship between TNF production in the brain and alpha2-adrenergic receptor activation could have profoun...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20407
更新日期:2005-03-15 00:00:00
abstract::The distribution of neuronal intermediate filament proteins in the developing mouse olfactory bulb and olfactory epithelium was characterized by immunocytochemical approach. Antibodies against alpha-internexin, neurofilament triplet proteins (NFTPs; NF-L, NF-M, and NF-H) and peripherin were used to determine their exp...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4547(19981101)54:3<353::AID-JNR
更新日期:1998-11-01 00:00:00
abstract::Remyelination of the central nervous system in multiple sclerosis patients is often incomplete. Remyelination depends on normal oligodendrogenesis and the differentiation of oligodendrocyte precursor cells (OPC) into mature oligodendrocytes (OL). Inhibitor of DNA binding (ID), a transcription factor, is thought to inh...
journal_title:Journal of neuroscience research
pub_type: 杂志文章,评审
doi:10.1002/jnr.22826
更新日期:2012-05-01 00:00:00
abstract::Mannitol, which is a cell-impermeable and nontoxic polyalcohol, has been shown to be a useful tool for reversible opening of the blood-brain barrier (BBB). Despite successful clinical trials, the molecular mechanism of the mannitol-induced changes in cerebral endothelial cells (CECs) are poorly understood. For our exp...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20521
更新日期:2005-06-15 00:00:00
abstract::Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therape...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.24253
更新日期:2018-08-01 00:00:00
abstract::In our in vitro model, rasagiline a selective irreversible monoamine oxidase-B (MAO-B) inhibitor, protected nerve growth factor (NGF)-differentiated PC12 cells from cell death under oxygen and glucose deprivation (OGD). The severity of the OGD insult, as expressed by cell death, was time-dependent. Exposure of the cel...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::The location of glyoxylate-complex molecules has been investigated in several areas of the rat cerebral cortex using the immunohistochemical peroxidase-antiperoxidase (PAP) method. Antibodies against glyoxylate-complex molecules have been developed in the rabbit after immunization with a glyoxylate-bovine serum albumi...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4547(19980115)51:2<268::AID-JNR
更新日期:1998-01-15 00:00:00
abstract::Monitoring pathology/regeneration in experimental models of de-/remyelination requires an accurate measure not only of functional changes but also of the amount of myelin. We tested whether X-ray diffraction (XRD), which measures periodicity in unfixed myelin, can assess the structural integrity of myelin in fixed tis...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.22241
更新日期:2010-03-01 00:00:00
abstract::In Alzheimer's disease, Aβ deposits are considered the initial cardinal events that induce tauopathy secondarily. However, the relationship between Aβ amyloidosis and tauopathy has not been determined in detail. We produced double transgenic mice, 2×TgTau(+/-) APP(+/-) , by mating Tg2576 mice that exhibit Aβ amyloidos...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.22516
更新日期:2010-12-01 00:00:00