Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson's disease

Eve, David J.; Nisbet, Angus; Kingsbury, Ann; Hewson, Louise; Daniel, Susan E.; Lees, Andrew J.; Marsden, C. D.; Föster, O

doi:10.1016/s0169-328x(98)00259-9

Cited by 109 publications

(73 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inducible NOS isoform, NOS2, has received considerable attention due to the capacity of this enzyme to produce levels of NO at concentrations that are cytotoxic to surrounding neurons and because deletion of the Nos2 gene confers partial neuroprotection in the MPTP model of PD (Liberatore et al, 1999). However, studies also indicate the importance of the constitutively expressed neuronal isoform, NOS1, in the progression of human PD (Eve et al, 1998) and in MPTP-induced neuropathology in animal models (Przedborski et al, 1996;Watanabe et al, 2004). Unlike Nos2, deletion of Nos1 in mice confers nearly complete protection against MPTP neurotoxicity (Przedborski et al, 1996) but the underlying reason for this observation remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Studies exploring pathophysiologic expression of NOS have typically focused on the inducible isoform (NOS2) but induction of the constitutively expressed neuronal nitric oxide synthase (NOS1) has emerged as an underlying component of a diverse array of neurologic disorders, including ischemic cerebral injury (e.g. stroke) (Moro et al, 2004), substance-induced neurological dysfunction including alcohol and methamphetamine abuse (Imam et al, 2001), as well as idiopathic neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer's disease, and PD (Catania et al, 2001;Chabrier et al, 1999;Eve et al, 1998). Underscoring a role for this enzyme in the progression of PD is the observation that ablation of the Nos1 gene in the 1-methyl-MPTP model of parkinsonism completely prevents neurotoxicity (Przedborski et al, 1996), as well as additional studies demonstrating protection of dopaminergic neurons in MPTP-treated mice by the NOS1-specific inhibitor 7-nitroindazole (7-NI) (Watanabe et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nuclear factor kappa-B mediates selective induction of neuronal nitric oxide synthase in astrocytes during low-level inflammatory stimulation with MPTP

2008

View full text Add to dashboard Cite

Recent advances in understanding the progression of Parkinson's disease (PD) implicate perturbations in astrocyte function and induction of constitutively expressed neuronal nitric oxide synthase (NOS1) in both human PD and in the MPTP model of the disease. Transcriptional regulation of NOS1 is complex but recent data suggest that nuclear factor kappa B (NF-κB) is an important transcription factor involved in inducible expression of the gene. The data presented here demonstrate that mild activation of primary astrocytes with low or 'sub-optimal' concentrations of MPTP (1 µM) and the inflammatory cytokines tumor necrosis factor alpha (10 pg/ml) and interferon gamma (1 ng/ ml) results in selective induction of Nos1 mRNA and protein, increased production of nitric oxide (NO), and a significant elevation in global protein nitration. This mild inflammatory stimulus also resulted in activation and recruitment of p65 to a putative NF-κB response element located in the Nos1 promoter region flanking exon 1. A role for NF-κB in MPTP-dependent induction of NOS1 was confirmed through overexpression of a mutant IκBα super repressor of NF-κB that prevented induction of NOS1. The data presented here thus demonstrate a role for NF-κB in selective induction of NOS1 during early inflammatory activation of astrocytes stimulated by low-dose MPTP and inflammatory cytokines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear factor kappa-B mediates selective induction of neuronal nitric oxide synthase in astrocytes during low-level inflammatory stimulation with MPTP

2008

View full text Add to dashboard Cite

show abstract

“…This may have functional implications, since it is the internal segment of the GP (GPi) and not the GPe that relays the basal ganglia output to the motor nuclei of the thalamus. In the GP, NO is probably co-localized with GABA, which has previously been shown to be the neurotransmitter of virtually all pallidal neurons (Nisbet et al 1994;Eve et al 1998). …”

Section: Nitric Oxide Distribution In the Basal Gangliamentioning

confidence: 93%

“…The pharmacological blocking of nNOS decreases locomotion and induces catalepsy in different animal species [see Del Bel et al (2007) for a review]. Although NOS neurons are present throughout all basal ganglia nuclei and in other regions involved in motor control such as the motor cortices and the pedunculopontine tegmental nucleus (PPTg), their concentration varies significantly (Bredt et al 1990;Del Bel et al 2007;Egberongbe et al 1994;Eve et al 1998;Garthwaite and Boulton 1995;Leontovich et al 2004;Nisbet et al 1994;Vincent and Kimura 1992).…”

Section: Nitric Oxide Distribution In the Basal Gangliamentioning

confidence: 99%

“…The NOS expression in the striatum has been more extensively studied (Bernácer et al 2005;Egberongbe et al 1994;Eve et al 1998;Govsa and Kayalioglu 1999;Johannes et al 2003;Leontovich et al 2004;Nisbet et al 1994;Vincent and Kimura 1992). NOS neurons are one type of the four different classes of interneurons present in the striatum, and in the human they populate the entire striatum, including the tail and head of the caudate nucleus.…”

Section: Nitric Oxide Distribution In the Basal Gangliamentioning

confidence: 99%

See 1 more Smart Citation

Nitric Oxide Modulation of the Dopaminergic Nigrostriatal System: Focus on Nicotine Action

Matteo

Pierucci

Benigno

et al. 2009

Advances in Behavioral Biology

View full text Add to dashboard Cite

Nitric oxide (NO) signalling plays an important role in the integration of information processed by the basal ganglia nuclei. Accordingly, considerable evidence has emerged indicating a role for NO in pathophysiological conditions such as Parkinson's disease (PD), schizophrenia and drug addiction. To further investigate the NO modulation of dopaminergic function in the basal ganglia circuitry, in this study we used in vivo electrophysiology and microdialysis in freely-moving rats. Pharmacological manipulation of the NO system did not cause any significant changes either in the basal firing rate and bursting activity of the dopamine (DA) neurons in the substantia nigra pars compacta (SNc) or in DA release in the striatum. In contrast, the disruption of endogenous NO tone was able to counteract the phasic dopaminergic activation induced by nicotine treatment in both experimental approaches. These results further support the possibility that nicotine acts via a NO mechanism and suggest a possible state-dependent facilitatory control of NO on the nigrostriatal DA pathway. Thus, NO selectively modulates the DA exocytosis associated with increased DA function.

show abstract

Intensity of GABA‐evoked responses is modified by nitric oxide‐active compounds in the subthalamic nucleus of the rat: A microiontophoretic study

Sardo

Carletti

D’Agostino

et al. 2009

J of Neuroscience Research

View full text Add to dashboard Cite

We have previously described modulatory effects of nitric oxide (NO)-active drugs on subthalamic nucleus (STN) neurons. In this study, the effects of microiontophoretically applied NO-active compounds on GABA-evoked responses were investigated in subthalamic neurons extracellularly recorded from anesthetized rats: 45 of 62 cells were excited by S-nitroso-glutathione (SNOG), an NO donor, whereas 28 of 43 neurons were inhibited by Nomega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Nearly all neurons responding to SNOG and/or L-NAME showed significant inhibitory responses to the administration of iontophoretic GABA. In these cells, the changes induced by NO-active drugs in the magnitude of GABA-evoked responses were used as indicators of NO modulation. In fact, when an NO-active drug was co-iontophoresed with GABA, significant changes in GABA-induced responses were observed: generally, decreased magnitudes of GABA-evoked responses were observed during continuous SNOG ejection, whereas the administration of L-NAME enhanced GABA responses. In contrast, glutamate-evoked responses were enhanced by SNOG and dampened by L-NAME co-iontophoresis. Furthermore, the iontophoretic administration of bicuculline (a GABA(A) receptor antagonist) completely abolished the GABA-evoked inhibitory responses and reduced the magnitude of both the SNOG- and L-NAME-induced effects. The results suggest that the NO-mediated modulation of subthalamic neurons could also be a result of an interaction between NO and GABA(A) neurotransmission. Increased NOS activity has been shown in the hyperactive STN neurons of parkinsonian patients; on the basis of our observations about the influence of NO-active drugs on the baseline and GABA-evoked activity of subthalamic cells, such hyperactivity suggests the involvement of increased NO levels and reduced sensitivity to GABA.

show abstract

Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson's disease

Cited by 109 publications

References 41 publications

Nuclear factor kappa-B mediates selective induction of neuronal nitric oxide synthase in astrocytes during low-level inflammatory stimulation with MPTP

Nuclear factor kappa-B mediates selective induction of neuronal nitric oxide synthase in astrocytes during low-level inflammatory stimulation with MPTP

Nitric Oxide Modulation of the Dopaminergic Nigrostriatal System: Focus on Nicotine Action

Intensity of GABA‐evoked responses is modified by nitric oxide‐active compounds in the subthalamic nucleus of the rat: A microiontophoretic study

Contact Info

Product

Resources

About