Species, strain and developmental variations in hippocampal neuronal and endothelial nitric oxide synthase clarify discrepancies in nitric oxide-dependent synaptic plasticity

Blackshaw, Seth; Eliasson, Mikael J. L.; Sawa, Akira; Watkins, Crystal C.; Krug, David K.; Gupta, Ashish; Arai, T.; Ferrante, Robert J.; Snyder, Solomon H.

doi:10.1016/s0306-4522(03)00217-3

Cited by 106 publications

(99 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 B). The stellate appearance of the majority of nNOS-positive cells corresponding to type I suggested that they were likely interneurons, which is in line with previous findings in the rat hippocampus (Valtschanoff et al, 1993;Blackshaw et al, 2003). However, a few pyramidal-shaped neurons were also present (Fig.…”

Section: Nos Activity In Rat Hippocampal Slice Culturessupporting

confidence: 91%

“…Because expression of nNOS in the entorhinal cortex is higher in rats than in mice (Blackshaw et al, 2003), we investigated whether the NO formation was still relevant for development and maintenance of epileptiform activity in the mouse entorhinal cortex. Under lowMg 2ϩ condition, SLEs developed in 89% (n ϭ 27) ( Fig.…”

Section: Effects Of No Deprivation On Epileptiform Activity In Hippocmentioning

confidence: 99%

“…To determine the direct effects of NO on seizure initiation, we chose an in vitro model of epilepsy, in which NO-dependent changes in tissue oxygenation were absent. Because previous controversial results might be ascribed to regional and interspecies differences in NO formation (Blackshaw et al, 2003), we compared the regulatory role of NO on epileptiform activity in different preparations from hippocampus and entorhinal cortex of rats and mice.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

Kovacs¹,

Rabanus²,

Otáhal³

et al. 2009

Journal of Neuroscience

View full text Add to dashboard Cite

Nitric oxide (NO) modulates synaptic transmission, and its level is elevated during epileptic activity in animal models of epilepsy. However, the role of NO for development and maintenance of epileptic activity is controversial. We studied this aspect in rat organotypic hippocampal slice cultures and acute hippocampal-entorhinal cortex slices from wild-type and neuronal NO synthase (nNOS) knock-out mice combining electrophysiological and fluorescence imaging techniques. Slice cultures contained nNOS-positive neurons and an elaborated network of nNOS-positive fibers. Lowering of extracellular Mg 2ϩ concentration led to development of epileptiform activity and increased NO formation as revealed by NO-selective probes, 4-amino-5-methylamino-2Ј,7Ј-difluorofluorescein and 1,2-diaminoanthraquinone sulfate. NO deprivation by NOS inhibitors and NO scavengers caused depression of both EPSCs and IPSCs and prevented initiation of seizure-like events (SLEs) in 75% of slice cultures and 100% of hippocampal-entorhinal cortex slices. This effect was independent of the guanylyl cyclase/cGMP pathway. Suppression of SLE initiation in acute slices from mice was achieved by both the broad-spectrum NOS inhibitor N-methyl-L-arginine acetate and the nNOS-selective inhibitor 7-nitroindazole, whereas inhibition of inducible NOS by aminoguanidine was ineffective, suggesting that nNOS activity was crucial for SLE initiation. Additional evidence was obtained from knock-out animals because SLEs developed in a significantly lower percentage of slices from nNOS Ϫ/Ϫ mice and showed different characteristics, such as prolongation of onset latency and higher variability of SLE intervals. We conclude that enhancement of synaptic transmission by NO under epileptic conditions represents a positive feedback mechanism for the initiation of seizure-like events.

show abstract

Section: Nos Activity In Rat Hippocampal Slice Culturessupporting

confidence: 91%

Section: Effects Of No Deprivation On Epileptiform Activity In Hippocmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

Kovacs¹,

Rabanus²,

Otáhal³

et al. 2009

Journal of Neuroscience

View full text Add to dashboard Cite

show abstract

“…NO is generated from arginine by nitric oxide synthases (NOS-I, NOS-II, and NOS-III) (Forstermann et al, 1991;Moncada et al, 1991;Bredt and Snyder, 1992). The calcium-dependent neuronal NOS (nNOS or NOS-I) is expressed in both a subpopulation of hippocampal interneurons Kosaka, 2002, 2004) and pyramidal cells (Wendland et al, 1994;Blackshaw et al, 2003), in which it can contribute to LTP (Doyle et al, 1996;Hawkins et al, 1998;Zorumski and Izumi, 1998;Bon and Garthwaite, 2003). nNOS binds to PDZ /Discs large/Zona occludens-1]-domain-containing scaffold proteins in excitatory postsynaptic densities (Christopherson et al, 1999;Tochio et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Szabadits¹,

Cserép²,

Ludányi³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Nitric oxide (NO) plays an important role in synaptic plasticity as a retrograde messenger at glutamatergic synapses. Here we describe that, in hippocampal pyramidal cells, neuronal nitric oxide synthase (nNOS) is also associated with the postsynaptic active zones of GABAergic symmetrical synapses terminating on their somata, dendrites, and axon initial segments in both mice and rats. The NO receptor nitric oxide-sensitive guanylyl cyclase (NOsGC) is present in the brain in two functional subunit compositions: ␣ 1 ␤ 1 and ␣ 2 ␤ 1 . The ␤ 1 subunit is expressed in both pyramidal cells and interneurons in the hippocampus. Using immunohistochemistry and in situ hybridization methods, we describe that the ␣ 1 subunit is detectable only in interneurons, which are always positive for ␤ 1 subunit as well; however, pyramidal cells are labeled only for ␤ 1 and ␣ 2 subunits. With double-immunofluorescent staining, we also found that most cholecystokinin-and parvalbumin-positive and smaller proportion of the somatostatin-and nNOS-positive interneurons are ␣ 1 subunit positive. We also found that the ␣ 1 subunit is present in parvalbumin-and cholecystokinin-positive interneuron terminals that establish synapses on somata, dendrites, or axon initial segments. Our results demonstrate that NOsGC, composed of ␣ 1 ␤ 1 subunits, is selectively expressed in different types of interneurons and is present in their presynaptic GABAergic terminals, in which it may serve as a receptor for NO produced postsynaptically by nNOS in the very same synapse.

show abstract

“…The accepted view of exclusive expression of nNOS in neurons and eNOS in endothelium of capillaries and large vessels (7,(35)(36)(37) was recently confirmed by quantitative RNA sequencing (38), a technique that in addition revealed substantial endothelial mRNA expression of iNOS, the isoform with the highest capacity for NO production and previously thought to be expressed only under pathological conditions. In contrast, almost no transcripts for nNOS, eNOS, or iNOS were detected in astrocytes, oligodendrocytes, oligodendrocyte precursor cells, or microglia.…”

Section: Sources and Concentration Of No In Brain Tissuementioning

confidence: 91%

Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

Martín

Arce-Molina

Galaz

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling.In brain tissue and retina, NO contributes to both vasodilation and vasoconstriction (1, 2). The vasoactive effects of NO are mediated by the enzymes guanylate cyclase, cytochrome P450 epoxygenase, and -hydroxylase, which sense different NO concentrations. Guanylate cyclase is stimulated in the picomolar to low nanomolar range, whereas cytochrome P450 enzymes are inhibited at tens to hundreds of nanomolar NO (1, 3). However, there is more to NO than vasodilation. Endothelial cells express both endothelial NO synthase (eNOS) 3 and inducible NO synthase (iNOS) (4) resulting in NO production strong enough to sustain up to 70 nM extracellular NO in response to shear stress (5), to reach cells millimeters away in bicameral cultures (6), or to permeate across layers of astrocytes and myelin toward axons in vivo (7). A fourth well characterized molecular target of NO is mitochondrial cytochrome oxidase (EC 1.9.3.1), whose sensitivity to NO is similar to that of cytochrome P450 (8, 9). As inhibition of cytochrome oxidase reduces local oxygen consumption, endothelial NO has been proposed to extend the effective zone of oxygenation away from the vessel (10). A role for NO-dependent mitochondrial inhibition in brain tissue was suggested upon the observation that NO inhibits astrocytic respiration, resulting in stimulated glycolysis and lactate production (11, 12). Conceivably, inhibition of cytochrome oxidase may not only play a tonic distributive role but may also participate in activity-dependent neurometabolic coupling (13). However, there are aspects that need further exploring, notably the speed and potency of the metabolic effects in the face of actual NO concentrations found under...

show abstract

Species, strain and developmental variations in hippocampal neuronal and endothelial nitric oxide synthase clarify discrepancies in nitric oxide-dependent synaptic plasticity

Cited by 106 publications

References 51 publications

Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

Contact Info

Product

Resources

About