Hydrogen Peroxide Modulation of Synaptic Plasticity

Kamsler, Ariel; Segal, Menahem

doi:10.1523/jneurosci.23-01-00269.2003

Cited by 179 publications

(160 citation statements)

References 43 publications

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“…24 Following hyperoxia, we detected an acute and long-term dysregulation of SYN1, a protein that regulates nerve terminal function in mature synapses and also affects axonogenesis and synaptogenesis. 26 While the acute dysregulation of SYN1 may be interpreted as secondary to a depletion of synaptic vesicles, the increase in abundance of two isospots of this protein 4 weeks following hyperoxia suggests a long-term disruption of normal synaptic function.…”

Section: Synaptic Function and Vesicle Traffickingmentioning

confidence: 94%

“…In the mature brain, oxidative stress modulates neuronal excitability and morphological features of synapses: 24,25 while low levels of hydrogen peroxide seem to prime synapses and induce long-term potentiation (LTP), high levels of ROS have detrimental effects on neuronal plasticity and suppress LTP in hippocampal slices of rats and mice. 24 Following hyperoxia, we detected an acute and long-term dysregulation of SYN1, a protein that regulates nerve terminal function in mature synapses and also affects axonogenesis and synaptogenesis.…”

Section: Synaptic Function and Vesicle Traffickingmentioning

confidence: 99%

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Acute and long-term proteome changes induced by oxidative stress in the developing brain

et al. 2005

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The developing mammalian brain experiences a period of rapid growth during which various otherwise innocuous environmental factors cause widespread apoptotic neuronal death. To gain insight into developmental events influenced by a premature exposure to high oxygen levels and identify proteins engaged in neurodegenerative and reparative processes, we analyzed mouse brain proteome changes at P7, P14 and P35 caused by an exposure to hyperoxia at P6. Changes detected in the brain proteome suggested that hyperoxia leads to oxidative stress and apoptotic neuronal death. These changes were consistent with results of histological and biochemical evaluation of the brains, which revealed widespread apoptotic neuronal death and increased levels of protein carbonyls. Furthermore, we detected changes in proteins involved in synaptic function, cell proliferation and formation of neuronal connections, suggesting interference of oxidative stress with these developmental events. These effects are age-dependent, as they did not occur in mice subjected to hyperoxia in adolescence.

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Section: Synaptic Function and Vesicle Traffickingmentioning

confidence: 94%

Section: Synaptic Function and Vesicle Traffickingmentioning

confidence: 99%

Acute and long-term proteome changes induced by oxidative stress in the developing brain

et al. 2005

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“…In contrast, others have shown that rapamycin impairs LTP by inhibiting mTOR through reduced protein synthesis (Casadio et al, 1999;Tang et al, 2002). Finally, a third study demonstrated that rapamycin did not affect LTP at baseline, and did not prevent the inhibition of LTP by H 2 O 2 (20 µM) (Kamsler and Segal, 2003).…”

Section: Introductionmentioning

confidence: 94%

Effects of rapamycin on gene expression, morphology, and electrophysiological properties of rat hippocampal neurons

et al. 2007

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SummaryPurpose-We assayed the effects of rapamycin, an immunomodulatory agent known to inhibit the activity of the mammalian target of rapamycin (mTOR) cascade, on candidate gene expression and single unit firing properties in cultured rat hippocampal neurons as a strategy to define the effects of rapamycin on neuronal gene transcription and excitability.Methods-Rapamycin was added (100 nM) to cultured hippocampal neurons on days 3 and 14. Neuronal somatic size and dendritic length were assayed by immunohistochemistry and digital imaging. Radiolabeled mRNA was amplified from single hippocampal pyramidal neurons and used to probe cDNA arrays containing over 100 distinct candidate genes including cytoskeletal element, growth factor, transcription factor, neurotransmitter, and ion channel genes. In addition, the effects of rapamycin (200 nM) on spontaneous neuronal activity and voltage-dependent currents was assessed.Results-There were no effects of rapamycin on cell size or dendrite length. Rapamycin altered expression of distinct mRNAs in each gene family on days 3 and 14 in culture. Single unit recordings from neurons exposed to rapamycin exhibited no change from baseline. When spontaneous activity was increased by blocking GABA-mediated inhibition with bicuculline, a fraction of the neurons exhibited a decreased duration of spontaneous bursts and a decrease in synaptic inputs. Rapamycin did not appear to alter voltage dependent Na+ or K+ currents underlying action potentials.Conclusions-These data demonstrate that rapamycin does not produce neurotoxicity nor alter dendritic growth and complexity in vitro and does not significantly alter voltage gated sodium and potassium currents. Rapamycin does affect neuronal gene transcription in vitro. Use of rapamycin in clinical trials for patients with tuberous sclerosis complex should involve vigilance for possible effects on seizure frequency and neurocognitive function.

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Section: Introductionmentioning

confidence: 99%

“…A low concentration of H 2 O 2 (1 M), a molecule that partially mediates superoxide-induced potentiation (Knapp and Klann 2002), increased the magnitude of LTP (Kamsler and Segal 2003). This effect was dependent on activation of L-type calcium channels but not NMDA receptors (Kamsler and Segal 2003). Furthermore, a functional coupling between RyRs and L-type calcium channels has been established in the dentate gyrus and cerebellar granule cells (Chavis et al 1996;Welsby et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Superoxide-Induced Potentiation in the Hippocampus Requires Activation of Ryanodine Receptor Type 3 and ERK

Huddleston

Tang

Takeshima

et al. 2008

Journal of Neurophysiology

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Huddleston AT, Tang W, Takeshima H, Hamilton SL, Klann E. Superoxide-induced potentiation in the hippocampus requires activation of tyanodine receptor type 3 and ERK. J Neurophysiol 99: 1565-1571, 2008. First published January 16, 2008 doi:10.1152/jn.00659.2007. Reactive oxygen species (ROS) are required for the induction of longterm potentiation (LTP) and behave as signaling molecules via redox modifications of target proteins. In particular, superoxide is necessary for induction of LTP, and application of superoxide to hippocampal slices is sufficient to induce LTP in area CA1. Although a rise in postsynaptic intracellular calcium is necessary for LTP induction, superoxide-induced potentiation does not require calcium flux through N-methyl-D-aspartate (NMDA) receptors. Ryanodine receptors (RyRs) mediate calcium-induced calcium release from intracellular stores and have been shown to modulate LTP. In this study, we investigated the highly redox-sensitive RyRs and L-type calcium channels as calcium sources that might mediate superoxide-induced potentiation. In agreement with previous studies of skeletal and cardiac muscle, we found that superoxide enhances activation of RyRs in the mouse hippocampus. We identified a functional coupling between L-type voltage-gated calcium channels and RyRs and identified RyR3, a subtype enriched in area CA1, as the specific isoform required for superoxide-induced potentiation. Superoxide also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) in area CA1, and ERK was necessary for superoxide-induced potentiation. Thus superoxide-induced potentiation requires the redox targeting of RyR3 and the subsequent activation of ERK.

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Hydrogen Peroxide Modulation of Synaptic Plasticity

Cited by 179 publications

References 43 publications

Acute and long-term proteome changes induced by oxidative stress in the developing brain

Acute and long-term proteome changes induced by oxidative stress in the developing brain

Effects of rapamycin on gene expression, morphology, and electrophysiological properties of rat hippocampal neurons

Superoxide-Induced Potentiation in the Hippocampus Requires Activation of Ryanodine Receptor Type 3 and ERK

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