Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat

Zhou, Lihua; Wu, Wutian

doi:10.1016/j.expneurol.2005.08.019

Cited by 37 publications

(41 citation statements)

References 55 publications

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“…Because the specificity of the present nNOS AS-ODN was shown to be effective in inhibiting nNOS enzyme activity in spinal motoneurons in vivo in our previous study (Zhou and Wu, 2006), we tested AS-ODN effects on both nNOS protein and nNOS mRNA levels in cultured CGNs. AS-ODN at 8 mM was added to CGNs at 7 DIC for 72 hr, with 8 mM R-ODN and the same volume of TE-buffer as controls.…”

Section: Antisense Odn Downregulated Nnos Gene In Cultured Cgns In Mamentioning

confidence: 99%

“…No positive matches were produced for the R-ODN. According to our previous study (Zhou and Wu, 2006), a concentration of 8 mM FITC-R-ODN was applied to CGNs at 7 DIC and imaged under a fluorescence microscope to detect the uptake of ODNs by cultured CGNs. The 72 hr was set as the optimal transfaction time of antisense oligos.…”

Section: Culture Treatments With Antisense Odnsmentioning

confidence: 99%

“…Recently, AS-ODN has been used to explore the molecular events or signal pathways induced by functional gene expression in neuronal development (Formisano et al, 2007;Huh et al, 2008;Li et al, 2008). We also used AS-ODN in vivo to explore the molecular mechanisms of nNOS in motoneuron death (Zhou and Wu, 2006). In the present study, the same AS-ODN strategy was used to study the role of endogenous nNOS in CGNs development.…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro

Wang

Peng

et al. 2010

Developmental Dynamics

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The role of endogenous neuronal nitric oxide synthase (nNOS) gene in the development of cerebellar granule neurons (CGNs) is conflicting. Here, we tested the effect of antisense oligos (AS-ODN) on the endogenous nNOS gene and the development of the CGNs in vitro. The expression of nNOS increased in a development-dependent pattern both in terms of mRNA and protein. AS-ODN down-regulated nNOS gene, but in a posttranscriptional manner. Knockdown of nNOS protein decreased the viability of the CGNs from 7 to 13 days in culture (DIC). This activity of AS-ODN was mimicked by nNOS inhibitor I. The antagonist (nNOSi, MK-801, or ODQ) -induced decrease of cell viability was normalized by the provision of the sodium nitroprusside, an NO donor. This study provides direct evidence that endogenous nNOS, mainly by means of its principal product NO, plays an active role in sustaining the survival of developing CGNs at transition from differentiation to maturation. Developmental Dynamics 239:474-481,

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Section: Antisense Odn Downregulated Nnos Gene In Cultured Cgns In Mamentioning

confidence: 99%

Section: Culture Treatments With Antisense Odnsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro

Wang

Peng

et al. 2010

Developmental Dynamics

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“…Nitric oxide (NO) and related RNS are a group of radicals linked with the secondary pathology of SCI [1,4,5]. There are close temporal correlations between the enhanced inducible nitric oxide synthase (iNOS) expression after injury and the death of NSC grafts [6][7][8] (i.e., within the first 12-72 h after injury), indicating a possible role for RNS radicals in triggering the cell graft loss.…”

Section: Introductionmentioning

confidence: 99%

“…While the detrimental and beneficial effects of the secondary reactions p.i. are still under debate [3][4][5], it is largely unknown as to how such neuroinflammatory events affect the survival and therapeutic potential of the undifferentiated neural stem cells (NSCs) in vivo. Because of the expression profile difference in surface receptors and intracellular targets between NSCs and mature tissue, the mechanisms underlying adult tissue loss may not be responsible for the acute donor NSC loss post transplantation.…”

Section: Introductionmentioning

confidence: 99%

Blockade of Peroxynitrite-Induced Neural Stem Cell Death in the Acutely Injured Spinal Cord by Drug-Releasing Polymer

Neeley²,

Pritchard³

et al. 2009

Stem Cells

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Therapeutic impact of neural stem cells (NSCs) for acute spinal cord injury (SCI) has been limited by the rapid loss of donor cells. Neuroinflammation is likely the cause. Since there are close temporal-spatial correlations between the inducible nitric oxide (NO) synthase expression and the donor NSC death after neurotrauma, we reasoned that NO-associated radical species might be the inflammatory effectors which eliminate NSC grafts and kill host neurons. To test this hypothesis, human NSCs (hNSCs: 5×10 4 -2×10 6 /ml) were treated in vitro with "plain" medium, 20 μM glutamate, or donors of NO and peroxynitrite (ONOO -; 100 and 400 μM of spermine or DETA NONOate, and SIN-1, respectively). hNSC apoptosis primarily resulted from SIN-1 treatment, showing ONOO --triggered protein nitration and the activation of p38 MAPK, cytochrome c release, and caspases. Therefore, cell death following post-SCI (p.i.) NO serge may be mediated NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript through conversion of NO into ONOO -. We subsequently examined such causal relationship in a rat model of dual penetrating SCI using a retrievable design of poly-lactic-co-glycolic acid (PLGA) scaffold seeded with hNSCs that was shielded by drug-releasing polymer. Besides confirming the ONOO --induced cell death signaling, we demonstrated that co-transplantation of PLGA film embedded with ONOO -scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or uric acid (1 μmol/film), markedly protected hNSCs 24 h p.i. (total: n = 10). Our findings may provide a bioengineering approach for investigating mechanisms underlying the host microenvironment and donor NSC interaction and help formulate strategies for enhancing graft and host cell survival after SCI.

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Local isoform‐specific NOS inhibition: A promising approach to promote motor function recovery after nerve injury

Moreno‐López

2010

J of Neuroscience Research

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Physical injury to a nerve is the most frequent cause of acquired peripheral neuropathy, which is responsible for loss of motor, sensory and/or autonomic functions. Injured axons in the peripheral nervous system maintain the capacity to regenerate in adult mammals. However, after nerve transection, stumps of damaged nerves must be surgically joined to guide regenerating axons into the distal nerve stump. Even so, severe functional limitations persist after restorative surgery. Therefore, the identification of molecules that regulate degenerative and regenerative processes is indispensable in developing therapeutic tools to accelerate and improve functional recovery. Here, I consider the role of nitric oxide (NO) synthesized by the three major isoforms of NO synthases (NOS) in motor neuropathy. Neuronal NOS (nNOS) seems to be the primary source of NO that is detrimental to the survival of injured motoneurons. Endothelial NOS (eNOS) appears to be the major source of NO that interferes with axonal regrowth, at least soon after injury. Finally, NO derived from inducible NOS (iNOS) or nNOS is critical to the process of lipid breakdown for Wallerian degeneration and thereby benefits axonal regrowth. Specific inhibitors of these isoforms can be used to protect injured neurons from degeneration and promote axonal regeneration. A cautious proposal for the treatment of acquired motor neuropathy using therapeutic tools that locally interfere with eNOS/nNOS activities seems to merit consideration.

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Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat

Cited by 37 publications

References 55 publications

Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro

Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro

Blockade of Peroxynitrite-Induced Neural Stem Cell Death in the Acutely Injured Spinal Cord by Drug-Releasing Polymer

Local isoform‐specific NOS inhibition: A promising approach to promote motor function recovery after nerve injury

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