Differential Susceptibility to Neurotoxicity Mediated by Neurotrophins and Neuronal Nitric Oxide Synthase

Samdani, Amer F.; Newcamp, Cheryl; Resink, Annelies; Facchinetti, Fabrizio; Hoffman, Brian E.; Dawson, Valina L.; Dawson, Ted M.

doi:10.1523/jneurosci.17-12-04633.1997

Cited by 91 publications

(65 citation statements)

References 78 publications

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“…In vivo models of cerebral ischemic preconditioning also do not support NMDA receptor-mediated production of nitric oxide (17,46). Possible reasons cited for negligible neuronal NOS expression in cortical culture (54), such as plating neurons on an established glial bed, cannot account for this discrepancy in the present cultures.…”

Section: Nitric Oxide-independent Preconditioningmentioning

confidence: 65%

Preconditioning of cortical neurons by oxygen-glucose deprivation: tolerance induction through abbreviated neurotoxic signaling

Tauskela

Brunette

Monette

et al. 2003

American Journal of Physiology-Cell Physiology

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Transient exposure of rat cortical cultures to nonlethal oxygen-glucose deprivation (OGD preconditioning) induces tolerance to otherwise lethal oxygen-glucose deprivation (OGD) or N-methyl-d-aspartate 24 h later. This study evaluates the role of cytosolic and mitochondrial Ca2+-dependent cellular signaling. Mechanistic findings are placed in context with other models of ischemic preconditioning or known neurotoxic pathways within cortical neurons. Tolerance to otherwise lethal OGD is suppressed by performing OGD preconditioning in the presence of the broad-scope catalytic antioxidants Mn(III)tetra(4-carboxyphenyl)porphyrin (MnTBAP) or Zn(II)tetra(4-carboxyphenyl)porphyrin [Zn(II)TBAP], but not by a less active analog, Mn(III)tetra(4-sulfonatophenyl)porphyrin, or a potent superoxide scavenger, Mn(III)tetra( N-ethyl-2-pyridyl)porphyrin chloride. Inhibitors of adenosine A1 receptors, nitric oxide synthase, mitogen-activated protein kinase, and poly(ADP-ribose) polymerase fail to suppress OGD preconditioning despite possible links with reactive oxygen species in other models of ischemic preconditioning. Preconditioning is suppressed by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), which has been ascribed elsewhere to inhibition of superoxide transport to the cytosol through mitochondrial anion channels. However, although it induces mitochondrial Ca2+ uptake, neuronal preconditioning is largely insensitive to mitochondrial uncoupling with carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone or 2,4-dinitrophenol. Un-couplers will prevent production of mitochondrial reactive oxygen species, implying nonmitochondrial targets by MnTBAP, Zn(II)TBAP, and DIDS. Emphasizing the importance of an increase in cytosolic Ca2+ during preconditioning, a Ca2+/calmodulin-dependent protein kinase II inhibitor, KN-62, suppresses development of subsequent tolerance. Summarizing, only those cellular transduction pathways that have the potential to be neurotoxic may be activated by preconditioning in cortical neurons. Finally, a marked decrease in extracellular glutamate is observed during otherwise lethal OGD in preconditioned cultures, suggesting that this end effector may represent a point of convergence across different preconditioning models.

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Section: Nitric Oxide-independent Preconditioningmentioning

confidence: 65%

Preconditioning of cortical neurons by oxygen-glucose deprivation: tolerance induction through abbreviated neurotoxic signaling

Tauskela

Brunette

Monette

et al. 2003

American Journal of Physiology-Cell Physiology

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“…Marmigere et al, 2003), whereas LPS and stress activate glutamatergic (Karreman and Moghaddam, 1996;Glezer et al, 2003) and dopaminergic (Abekawa et al, 2000;Gamaro et al, 2003;Matsumoto et al, 2005) systems, which induces BDNF expression (Zafra et al, 1990(Zafra et al, , 1991Kuppers and Beyer, 2001). Although BDNF increases in pathological situations (Felderhoff-Mueser et al, 2002) and seems to exert a protective activity (TapiaArancibia et al, 2004), some evidence suggests that neurotrophins strengthen or may even cause neuronal damage under certain pathological conditions through the induction of NADPH-oxidase (Koh et al, 1995;Samdani et al, 1997;Kim et al, 2002). Thus, BDNF could be involved in the increase of the damage induced by inflammation in stressed animals.…”

Section: Discussionmentioning

confidence: 99%

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Pablos¹,

Villarán²,

Argüelles³

et al. 2006

J. Neurosci.

193

176

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Inflammation could be involved in some neurodegenerative disorders that accompany signs of inflammation. However, because sensitivity to inflammation is not equal in all brain structures, a direct relationship is not clear. Our aim was to test whether some physiological circumstances, such as stress, could enhance susceptibility to inflammation in the prefrontal cortex (PFC), which shows a relative resistance to inflammation. PFC is important in many brain functions and is a target for some neurodegenerative diseases. We induced an inflammatory process by a single intracortical injection of 2 g of lipopolysaccharide (LPS), a potent proinflammogen, in nonstressed and stressed rats. We evaluated the effect of our treatment on inflammatory markers, neuronal populations, BDNF expression, and behavior of several mitogen-activated protein (MAP) kinases and the transcription factor cAMP response element-binding protein. Stress strengthens the changes induced by LPS injection: microglial activation and proliferation with an increase in the levels of the proinflammatory cytokine tumor necrosis factor-␣; loss of cells such as astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and neurons, studied by neuronal-specific nuclear protein immunohistochemistry and GAD67 and NMDA receptor 1A mRNAs expression by in situ hybridization. A significant increase in the BDNF mRNA expression and modifications in the levels of MAP kinase phosphorylation were also found. In addition, we observed a protective effect from RU486 [mifepristone (11␤-[p-(dimethylamino)phenyl]-17␤-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)], a potent inhibitor of the glucocorticoid receptor activation. All of these data show a synergistic effect between inflammation and stress, which could explain the relationship described between stress and some neurodegenerative pathologies.

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“…Thus arises the question of how to reconcile the neuroprotective effect of activating p44͞42 MAP kinase reported in previous studies with the neuroprotective effect of inhibiting p44͞42 MAP kinase reported here. The finding that neurotrophins can exacerbate neuronal death under some circumstances may be relevant to this question (53)(54)(55). Neurotrophins protect cultured cortical neurons against apoptotic death induced by serum withdrawal, but in the same system, neurotrophins exacerbate necrotic death induced by either glucose-oxygen deprivation or the brief application of N-methyl-D-aspartate (54).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity

Murray

Alessandrini

Cole

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

216

150

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Excessive release of glutamate and the subsequent inf lux of calcium are associated with a number of neurological insults that result in neuronal death. The calcium-activated intracellular signaling pathways responsible for this excitotoxic injury are largely unknown. Here, we report that PD098059, a selective inhibitor of the calcium-activated p44͞42 mitogen-activated protein kinase (MAP kinase) pathway, reduces neuronal death in a cell-culture model of seizure activity. Dissociated hippocampal neurons grown chronically in the presence of kynurenate, a broad spectrum glutamatereceptor antagonist, and elevated amounts of magnesium exhibit intense seizure-like activity after the removal of these blockers of excitatory synaptic transmission. A 30-min removal of the blockers produced extensive neuronal death within 24 h as assayed by the uptake of trypan blue and the release of lactate dehydrogenase. Phospho-p44͞42 MAP kinase immunoreactivity after 30 min of seizure-like activity was present in many neuronal somata and dendrites as well as some synaptic terminals, consistent with both the presynaptic and postsynaptic effects of this pathway. The addition of PD098059 (40 M; EC 50 ‫؍‬ 10 M) during a 30-min washout of synaptic blockers inhibited the phosphorylation of p44͞42 MAP kinase and reduced both the trypan-blue staining (n ‫؍‬ 13) and the release of lactate dehydrogenase (n ‫؍‬ 16) by 73% ؎ 18% and 75% ؎ 19% (mean ؎ SD), respectively. The observed neuroprotection could be caused by an effect of PD098059 on seizure-like events or on downstream signaling pathways activated by the seizure-like events. Either possibility suggests a heretofore unknown function for the p44͞42 MAP kinase pathway in neurons.Stimulation of numerous cell-surface receptors leads to the activation of kinase cascades that integrate and amplify extracellular signals and transmit them to intracellular targets (1). Mitogen-activated protein kinases (MAP kinases), a family of serine͞threonine kinases, are activated by phosphorylation on threonine and tyrosine (2, 3). One subfamily of MAP kinases, known as extracellular signal-regulated kinase (ERK), is activated strongly by mitogens, including growth factors, leading to many cellular responses including proliferation and differentiation (4, 5). Two ERK isoforms, ERK1 (p44) and ERK2 (p42), are highly expressed in the brain; p42 is particularly enriched in the dendrites and somata of discrete neuronal populations including the hippocampus (4, 6). The function of p44͞42 MAP kinase in postmitotic, terminally differentiated neurons is unclear, although recent reports implicate these kinases in synaptic plasticity (7,8).Stimulation of glutamate receptors and influx of Ca 2ϩ are associated with excitotoxic injury (9, 10) and lead to the phosphorylation of p44͞42 MAP kinase in neurons (11-16).Several neurological insults that produce an excessive release of glutamate and neuronal death, including hypoglycemia, ischemia, and kainate-or bicuculline-induced seizures, also result in the phosphoryla...

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Differential Susceptibility to Neurotoxicity Mediated by Neurotrophins and Neuronal Nitric Oxide Synthase

Cited by 91 publications

References 78 publications

Preconditioning of cortical neurons by oxygen-glucose deprivation: tolerance induction through abbreviated neurotoxic signaling

Preconditioning of cortical neurons by oxygen-glucose deprivation: tolerance induction through abbreviated neurotoxic signaling

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity

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