Abstract:
:Parkinson's disease is a neurodegenerative disorder associated with selective loss of the dopaminergic neurons in the substantia nigra. We have previously shown that tetrahydrobiopterin (BH4), the obligatory cofactor for dopamine synthesis, exerts selective toxicity on dopamine-producing cells. In the present study we determined, both in vitro and in vivo, whether the cell death induced by this endogenous molecule involves apoptosis, resembling that which occurs in Parkinson's disease. Transmission electron microscopic analysis revealed that the dopamine-producing CATH.a cells underwent ultrastructural changes typical of apoptosis, such as cell shrinkage and chromatin condensation, upon exposure to BH4. The BH4 treatment also caused intranuclear DNA fragmentation as determined by TUNEL staining. A similar phenomenon also occurred in vivo, as the nigral cells became TUNEL-positive upon injection of BH4 into the substantia nigra. The BH4-induced CATH.a cell death seemed to involve macromolecule synthesis because cycloheximide and actinomycin D had protective effects. Concurrent treatment with the caspase inhibitor Z-VAD-FMK also suppressed cell death. BH4 treatment led to increases in the ratio of Bax/Bcl-x(L) mRNA and protein levels. Ca(2+) seemed to play a role in BH4-induced cell death, because BH4 caused an increase in Ca(2+) uptake and the intracellular Ca(2+) release blocker dantrolene, intracellular Ca(2+) chelator BAPTA/AM, and extracellular Ca(2+) chelator EGTA each attenuated the toxicity. These data provide evidence that the dopaminergic cell death induced by BH4 involves apoptosis and suggest relevance of this cell death to degeneration of the dopaminergic system in Parkinson's disease.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Choi HJ,Kim SW,Lee SY,Moon YW,Hwang Odoi
10.1016/s0014-4886(03)00054-2keywords:
subject
Has Abstractpub_date
2003-06-01 00:00:00pages
281-90issue
2eissn
0014-4886issn
1090-2430pii
S0014488603000542journal_volume
181pub_type
杂志文章abstract::Human apolipoprotein E (apoE) is a 34.2kDa glycosylated protein with three isoforms (apoE2, apoE3 and apoE4). Experimental autoimmune neuritis (EAN), an animal model for human Guillain-Barré syndrome, is an immune-mediated experimental disorder of the peripheral nervous system (PNS). Increased susceptibility to EAN in...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.04.016
更新日期:2011-08-01 00:00:00
abstract::Spinal lamina II, where nociceptive C-fibers terminate, expresses high amounts of the polysialylated form of neural cell adhesion molecule (PSA-NCAM). While enzymatic removal of the PSA moiety from NCAM did not affect normal sensitivity to thermal stimuli, it exacerbated nerve injury-induced neuropathic hyperalgesia. ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.12.017
更新日期:2012-02-01 00:00:00
abstract::The focus of this study is the expression of Toll-like receptor-3 (TLR-3), a receptor for double-stranded RNA, in human brains affected by Alzheimer's disease (AD) pathology. Toll-like receptors are a family of pattern recognition molecules primarily involved in host defenses to microbial pathogens, but roles in neuro...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2018.07.016
更新日期:2018-11-01 00:00:00
abstract::Immune rejection of transplanted material is a potential complication of organ donation. In response to tissue transplantation, immune rejection has two components: a host defense directed against the grafted tissue and an immune response from the grafted tissue against the host (graft vs host disease). To treat immun...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(03)00128-6
更新日期:2003-08-01 00:00:00
abstract::Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozyg...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2013.09.019
更新日期:2013-12-01 00:00:00
abstract::Reactive synaptogenesis and terminal proliferation are known to occur in the dentate gyrus of the rat hippocampus following removal of specific afferents. In the present study we have examined the relation of synaptophysin immunoreactivity to the immunohistochemical staining pattern of GAP-43, a putative marker of neu...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(91)90169-d
更新日期:1991-08-01 00:00:00
abstract::Although prior studies have implicated maladaptive remodeling of dendritic spines on wide-dynamic range dorsal horn neurons as a contributor to pain after spinal cord injury, there have been no studies on dendritic spines after peripheral nerve injury. To determine whether dendritic spine remodeling contributes to neu...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.08.028
更新日期:2011-12-01 00:00:00
abstract::The tendency of a rat to approach the wall of an open-field and to travel along the perimeter of the field (termed as "peritaxis" or "wall-facing") is affected by unilateral removal of the vibrissae. Peritaxis is lateralized by hemivibrissotomy. The finding that the dopamine agonist apomorphine reversed the direction ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(88)90172-0
更新日期:1988-03-01 00:00:00
abstract::The monoclonal antibody Py has previously been shown to be a useful marker for subpopulations of neurons in the rat brain. However, the distribution of Py immunoreactivity in other regions of the CNS and PNS is not known. Here, we present a light and electron microscopic investigation into the distribution of Py immun...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6509
更新日期:1997-07-01 00:00:00
abstract::Recent evidence indicates that protein aggregation and in particular the formation of toxic protein oligomers is a key mechanism in synucleinopathies such as Parkinson's disease (PD). Post mortem brain tissue studies as well as animal studies furthermore suggest that matrix metalloproteinases (MMPs) are also involved ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.10.010
更新日期:2009-01-01 00:00:00
abstract::The purpose of this study was to assess the respiratory and tonic activity of the abdominal muscles and the postinspiratory activity of the diaphragm (stage 1 expiration) in rats during sleep while they breathed air, hypercapnic, and hypoxic gas mixtures. ECoG and neck EMG recordings enabled the differentiation to be ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(88)90064-7
更新日期:1988-07-01 00:00:00
abstract::Human immunodeficiency virus-associated distal-symmetric neuropathy (HIV-DSP) is the most common neurological complication of HIV infection. The pathophysiology of HIV-DSP is poorly understood and no treatment is available for this entity. The dorsal root ganglia (DRG) are the principal sites of neuronal damage and ar...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.06.015
更新日期:2008-03-01 00:00:00
abstract::After spinal cord injury (SCI), apoptosis of neurons and oligodendrocytes is associated with axonal degeneration and loss of neurological function. Recent data have suggested a potential role for FAS death receptor-mediated apoptosis in the pathophysiology of SCI. In this study, we examined the effect of FAS deficienc...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2005.08.020
更新日期:2005-12-01 00:00:00
abstract::Based on their differentiation ability, bone marrow stromal cells (MSCs) are a good source for cell therapy. Using a cynomolgus monkey peripheral nervous system injury model, we examined the safety and efficacy of Schwann cells induced from MSCs as a source for auto-cell transplantation therapy in nerve injury. Serial...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2010.01.022
更新日期:2010-06-01 00:00:00
abstract::Muscular dystrophies (MDs) consist of a genetically heterogeneous group of disorders, recessive or dominant, characterized by progressive skeletal muscle weakening. To date, no effective treatment is available. Experimental strategies pursuing muscle regeneration through the transplantation of stem cell preparations h...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2009.08.002
更新日期:2009-11-01 00:00:00
abstract::A previous study of our group demonstrated that movement performance induced by dopamine agonist drugs in hemiparkinsonian rats unilaterally lesioned with 6-hydroxydopamine (6-OHDA), governs the occurrence of a sensitized motor response to a subsequent dopaminergic challenge (priming model). In the present study, we e...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2013.03.002
更新日期:2013-09-01 00:00:00
abstract::Periodic changes in ovarian steroid levels during fertility cycles affect learning both in humans and in rats in parallel with electrophysiological and morphological fluctuations in selective neuronal populations. In particular, during the estrous cycle of the female rat, hippocampal CA1 region undergoes cyclic modifi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7186
更新日期:1999-10-01 00:00:00
abstract::Adeno-associated virus (AAV) vectors are derived from a nonpathogenic and defective human parvovirus. Although currently unable to display the integration specificity featured by its wild-type parent, the recombinant AAV (rAAV) system has continued to attract enormous interest primarily due to its unique features such...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1006/exnr.1996.6396
更新日期:1997-03-01 00:00:00
abstract::Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herei...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2018.02.016
更新日期:2018-06-01 00:00:00
abstract::Lead induces peripheral nerve segmental demyelination in rats. Arsenic and thallium produce a peripheral neuropathy characterized by axonal degeneration in humans. Mercury and thallium appear to damage both the peripheral and the central nervous system. It is not known whether this difference in effect is due to diffe...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(86)90283-9
更新日期:1986-10-01 00:00:00
abstract::We administered tetrahydroaminoacridine (THA), a cholinesterase inhibitor, to rats with bilateral nucleus basalis magnocellularis lesions and measured their performance in a spatial learning task. The subjects, 34 male Fischer-344 rats, received bilateral excitotoxic NBM lesions; 10 other rats served as unlesioned con...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(90)90126-d
更新日期:1990-06-01 00:00:00
abstract::Intracranial collaterals provide residual blood flow to penumbral tissue in acute ischemic stroke and contribute to infarct size variability in humans. In the present study, hemodynamic monitoring of the borderzone territory between the leptomeningeal branches of middle cerebral artery and anterior cerebral artery was...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.12.006
更新日期:2012-02-01 00:00:00
abstract::Pretreatment with the synthetic glucocorticoid dexamethasone prevents hypoxic-ischemic brain damage in 7-day-old neonatal rats. We presently characterize the response further by examining the effect of varying the age, the glucocorticoid, and the time of injection and by examining whether fasting can influence the res...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(95)90065-9
更新日期:1995-03-01 00:00:00
abstract::Local application of exogenous agents with neurotrophic properties enhances the regenerative capacity of injured neurons, especially following reconstructions of long nerve gaps and delayed nerve repairs. Recent advances in biomaterials and biomedical engineering have provided options for the sustained and controlled ...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2018.08.014
更新日期:2019-09-01 00:00:00
abstract::Sympathetic innervation of lymphoid tissues is localized to specific tissue compartments, but little is known of the "factors" that are important in establishing this pattern during development. Numerous studies have shown interactions of nerve growth factor (NGF) with the immune system, which may include modulation o...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6711
更新日期:1998-01-01 00:00:00
abstract::A host protein encoded by the gene specifying the scrapie amyloid precursor affects pathogenesis of the transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker's syndrome (GSS), and kuru in man, and scrapie in animals. We found a mutation in this gene of two patients ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(89)90095-2
更新日期:1989-11-01 00:00:00
abstract::We previously reported that 1 month following unilateral loss (>95%) of striatal dopamine, there is an increase in striatal glutamate function as measured by in vivo microdialysis and quantitative immuno-gold electron microscopy, Neuroscience 88, 1-16). The goal of this study was to determine the effect of bilateral l...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(02)00050-x
更新日期:2003-03-01 00:00:00
abstract::A "neuroplastic" hypothesis proposes that changes in neuronal structural plasticity may underlie the aetiology of depression and the action of antidepressants. The medial prefrontal cortex (mPFC) is affected by this disorder and shows an intense expression of the polysialylated form of the neural cell adhesion molecul...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.07.018
更新日期:2008-11-01 00:00:00
abstract::The neuronal basis for neurological deficits in infantile hydrocephalus is poorly understood. Changes in the dendritic architecture of pyramidal cells of the auditory cortex have been measured at 21 days after birth in H-Tx rats. Tissue was prepared by the rapid Golgi method from hydrocephalic and control litter-mates...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1996.0161
更新日期:1996-10-01 00:00:00
abstract::Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mulatta was accomplished using stereotactic injection of two distinct recombinant Ad5 vectors containing the gene for Escherichia coli beta-galactosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylphosphotransferase (HPRT), respectively. M...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1028
更新日期:1994-02-01 00:00:00