Localization of neuronal and endothelial nitric oxide synthase isoforms in human hippocampus

Doyle, Chris; Slater, P.

doi:10.1016/s0306-4522(96)00297-7

Cited by 104 publications

(65 citation statements)

References 43 publications

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“…The pattern of nNOS expression observed in the hippocampal formation and entorhinal cortex in the present study agrees with other reports (11,12). Although no quantitative description about the density of nNOS-IR neurons in the hippocampus has been previously reported, there appears to be a greater number of nNOS-IR neurons in the present study than reported by others.…”

Section: Discussionsupporting

confidence: 91%

“…Granular immunoreactivity was seen in the cytoplasm of nNOS-IR pyramidal neurons, showing the characteristic single apical dendrite projecting perpendicular to the axis of the hippocampus, as previously described by Doyle and Slater (12). The granule cells of the dentate gyrus were weakly immunostained for nNOS.…”

Section: Discussionsupporting

confidence: 75%

“…The human hippocampus contains a high density of NMDA receptors (10) and nNOS-expressing cells (11,12), suggesting the existence of an NMDA-NO transduction pathway. A crucial involvement of the NMDA-NO signaling pathway in the pathophysiology of MD and in the mechanism of action of antidepressant drugs has been suggested.…”

Section: Introductionmentioning

confidence: 99%

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Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders

Oliveira

Guimarães

Deakin

2008

Braz J Med Biol Res

110

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Hippocampal output is increased in affective disorders and is mediated by increased glutamatergic input via N-methyl-Daspartate (NMDA) receptor and moderated by antidepressant treatment. Activation of NMDA receptors by glutamate evokes the release of nitric oxide (NO) by the activation of neuronal nitric oxide synthase (nNOS). The human hippocampus contains a high density of NMDA receptors and nNOS-expressing neurons suggesting the existence of an NMDA-NO transduction pathway which can be involved in the pathogenesis of affective disorders. We tested the hypothesis that nNOS expression is increased in the human hippocampus from affectively ill patients. Immunocytochemistry was used to demonstrate nNOS-expressing neurons in sections obtained from the Stanley Consortium postmortem brain collection from patients with major depression (MD, N = 15), bipolar disorder (BD, N = 15), and schizophrenia (N = 15) and from controls (N = 15). nNOS-immunoreactive (nNOS-IR) and Nissl-stained neurons were counted in entorhinal cortex, hippocampal CA1, CA2, CA3, and CA4 subfields, and subiculum. The numbers of Nissl-stained neurons were very similar in different diagnostic groups and correlated significantly with the number of nNOS-IR neurons. Both the MD and the BD groups had greater number of nNOS-IR neurons/400 µm 2 in CA1 (mean ± SEM: MD = 9.2 ± 0.6 and BD = 8.4 ± 0.6) and subiculum (BD = 6.7 ± 0.4) when compared to control group (6.6 ± 0.5) and this was significantly more marked in samples from the right hemisphere. These changes were specific to affective disorders since no changes were seen in the schizophrenic group (6.7 ± 0.8). The results support the current view of the NMDA-NO pathway as a target for the pathophysiology of affective disorders and antidepressant drug development.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 75%

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Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders

Oliveira

Guimarães

Deakin

2008

Braz J Med Biol Res

110

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“…Using biochemical characterisation, neuronal NADPHdiaphorase has been equated with NOS (Hope et al, 1991) and NADPH-diaphorase histochemistry has historically been used to identify NOS activity. However, there is evidence (1) that not all NADPH-diaphorase activity is due to NOS (Worl et al, 1994) and (2) that some NOS does not exhibit NADPHdiaphorase activity (Wang et al, 1997;Doyle and Slater, 1997), raising questions as to the specificity of this technique for detecting all generic NOS activity. In addition, Nishikimi et al cultured embryos in KSOM (Nishikimi et al, 2001) whereas in the present study with DAF-FM, KSOM was supplemented with amino acids.…”

Section: Discussionmentioning

confidence: 99%

Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo

Manser

Houghton

2006

Journal of Cell Science

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Previous studies have demonstrated a role for the signalling agent nitric oxide in regulating preimplantation embryo development. We have now investigated the biochemical mode of action of nitric oxide in mouse embryos in terms of mitochondrial function and Ca2+ signalling. DETA-NONOate, a nitric oxide donor, decreased day 4 blastocyst cell number and oxygen consumption, consistent with a role for nitric oxide in the inhibition mitochondrial cytochrome c oxidase. Using live cell imaging and the nitric-oxide-sensitive probe DAF-FM diacetate, nitric oxide was detected at all stages of preimplantation development and FRET analysis revealed a proportion of the nitric oxide to be colocalised with mitochondria. This suggests that mitochondria of preimplantation embryos produce nitric oxide to regulate their own oxygen consumption. Inhibiting or uncoupling the electron transport chain induced an increase in nitric oxide and [Ca2+]i as well as disruption of Ca2+ deposits at the plasma membrane, suggesting that mitochondrial disruption can quickly compromise cellular function through Ca2+-stimulated nitric oxide production. A link between antimycin-A-induced apoptosis and nitric oxide signalling is proposed.

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“…What seems clear is that vascular NO is found in very high amounts in hippocampal pyramidal neurons, one of the principal and primary sites of AD pathology (Dinerman et al, 1994;Doyle and Slater, 1997;Kalaria, 2000).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes

Torre

Aliev

2005

J Cereb Blood Flow Metab

108

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An aging rat model of chronic brain hypoperfusion (CBH) that mimics human mild cognitive impairment (MCI) was used to examine the role of nitric oxide synthase (NOS) isoforms on spatial memory function. Rats with CBH underwent bilateral common carotid artery occlusion (2-vessel occlusion (2-VO)) for either 26 or 8 weeks and were compared with nonoccluded sham controls (S-VO). The neuronal and endothelial (nNOS/eNOS) constitutive inhibitor nitro-L-arginine methyl ester (L-NAME) 20 mg/kg was administered after 26 weeks for 3 days to 2-VO and S-VO groups and spatial memory was assessed with a modified Morris watermaze test. Only 2-VO rats worsened their spatial memory ability after L-NAME. Electron microscopic immunocytochemical examination using an antibody against eNOS showed 2-VO rats had significant loss or absence of eNOS-containing positive gold particles in hippocampal endothelium and these changes were associated with endothelial cell compression, mitochondrial damage and heavy amyloid deposition in hippocampal capillaries and perivascular region. In the 8-week study, three groups of 2-VO rats were administered an acute dose of 7-NI, aminoguanidine or L-NIO, the relatively selective inhibitors of nNOS, inducible NOS and eNOS. Only rats administered the eNOS inhibitor L-NIO worsened markedly their watermaze performance (P ¼ 0.009) when compared with S-VO nonoccluded controls. We conclude from these findings that vascular nitric oxide derived from eNOS may play a critical role in spatial memory function during CBH possibly by keeping cerebral perfusion optimal through its regulation of microvessel tone and cerebral blood flow and that disruption of this mechanism can result in spatial memory impairment. These findings may identify therapeutic targets for preventing MCI and treating Alzheimer's disease.

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Localization of neuronal and endothelial nitric oxide synthase isoforms in human hippocampus

Cited by 104 publications

References 43 publications

Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders

Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders

Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo

Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes

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