Nitric Oxide Synthase Activity in Brain Regions and Spinal Cord of Mice and Rats: Kinetic Analysis

Barjavel, Marc J.; Bhargava, Hemendra N.

doi:10.1159/000139279

Cited by 47 publications

(15 citation statements)

References 24 publications

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“…The results indicated that NOS in gonadectomized males and females was high in the cerebellum, the hypothalamus, and the amygdala with very low amounts in the cerebral cortex. These observations are similar to those reported by other investigators for male rats and mice (42).…”

Section: Discussionsupporting

confidence: 93%

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Singh¹

2000

Proceedings of the National Academy of Sciences

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Sex differences in nitric oxide synthase (NOS) activity in different regions of the rat brain and effects of testosterone and dihydrotestosterone (DHT) treatment in orchidectomized animals were investigated. Regional but no sex differences in NOS activity were detected in gonadectomized animals. Orchidectomy significantly increased NOS activity in the hypothalamus, ''amygdala,'' and cerebellum but not in the cortex. In the hypothalamus, the increase in NOS activity after castration and its reversal by androgen treatment was mimicked by changes in neuronal NOS mRNA level. In contrast, androgen receptor (AR) mRNA level in the hypothalamus was slightly reduced by castration and increased by treatment with DHT. Again in the hypothalamus, the increase in NOS activity in castrated rats was accompanied by an increase in the number of neuronal NOS؉ cells determined immunohistochemically, whereas androgen treatment prevented this increase. The changes in NOS؉ neurons correlated with the changes in the number of AR؉ cells to a degree. Overlap of AR in NOS؉ cells was not present in the regions of the hypothalamus analyzed. These results indicate that testosterone or, most likely, its metabolite DHT down-regulates NOS activity, mRNA expression or stabilization, and the number of neuronal NOS؉ neurons. N itric oxide (NO) synthesized by the enzyme neuronal nitric oxide synthase (nNOS) plays an important role in many brain functions. These include effects on long-term potentiation (1), gonadotropin secretion (2-10), and sexual behavior (11)(12)(13). NO functions as a neurotransmitter (2-10) and nNOS is present near gonadotropin-releasing hormone terminals (14) and in regions of the brain that appear to regulate emotional behaviors (15, 16). Estradiol (E 2 ) up-regulates endothelial NOS in endothelial cells (17,18) and nNOS in the brain (18-21), and many of the actions of E 2 on the brain have been suggested to be through a NO-mediated mechanism (2-10, 18-22). Administration of E 2 and progesterone to ovariectomized rats leads to an increase in the luteinizing hormone surge, the magnitude of which is significantly attenuated after administration of nNOS antisense oligonucleotides into the third ventricle (22), suggesting an intermediary role of NO in modulating some actions of E 2 by up-regulating nNOS activity.However, the actions of androgens on NOS activity in the brain are not clear. Male mice with targeted disruption of the nNOS gene (nNOS Ϫ ) display a great increase in aggressive behavior and excessive and inappropriate mounting behavior (11). Because androgens also promote aggressive behavior (23, 24), facilitate mounting behavior (25, 26), and decrease gonadotropin release (27, 28), we wanted to elucidate whether the androgens, testosterone (T) and its 5␣ reduced metabolite, dihydrotestosterone (DHT), modulate nNOS activity in the brain and the potential mechanism(s) by which this may occur.Therefore, sex-related and region-specific distributions of NOS in select regions of the rat brain of both sexes were assessed as ...

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Section: Discussionsupporting

confidence: 93%

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Singh¹

2000

Proceedings of the National Academy of Sciences

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“…45,46 Direct regional NOS assays also have demonstrated greater activity in the cortex and up to 50% higher striatal NOS activity than other brain regions. 7,47 In addition, other regions within the rat MCA distribution (hypothalamus, amygdala, and nucleus accumbens) 48 also have greater NOS concentrations than cortical structures. 7 Overall, the available data suggest that brain regions supplied by the MCA that form the ischemic core have greater NOS activity than the penumbra.…”

Section: Core and Penumbral Nos Activitymentioning

confidence: 99%

Core and Penumbral Nitric Oxide Synthase Activity During Cerebral Ischemia and Reperfusion

Ashwal

Tone

Tian

et al. 1998

Stroke

253

125

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Background and Purpose-The present studies examined the hypothesis that the distribution of cerebral injury after a focal ischemic insult is associated with the regional distribution of nitric oxide synthase (NOS) activity. Methods-Based on previous studies that certain anatomically well-defined areas are prone to become either core or penumbra after middle cerebral artery occlusion (MCAO), we measured NOS activity in these areas from the right and left hemispheres in a spontaneously hypertensive rat filament model. Four groups were studied: (1) controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5 hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of anesthesia and 1.5 hours of anesthesiaϩ24 hours of observation (S24). Results-Control core NOS activity for combined right and left hemispheres was 129% greater than penumbral NOS activity (PϽ0.05). Combined core NOS activity was also greater (PϽ0.05) in the three sham groups: 208%, 122%, and 161%, respectively. In the three MCAO groups, ischemic and nonischemic core NOS remained higher than penumbral regions (PϽ0.05). However, NOS activity was lower in the ischemic than in the nonischemic core in all three groups: R0 (29% lower), R0.5 (48%), and R24 (86%) (PϽ0.05). Addition of cofactors (10 mol/L tetrahydrobiopterin, 3 mol/L flavin adenine dinucleotide, and 3 mol/L flavin mononucleotide) increased NOS activity in all groups and lessened the decrease in ischemic core and penumbral NOS. Conclusions-Greater NOS activity in core regions could explain in part the increased vulnerability of that region to ischemia and could theoretically contribute to the progression of the infarct over time. The data also suggest that NOS activity during ischemia and reperfusion could be influenced by the availability of cofactors.

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“…Calmodulin is activated by calcium influx, which occurs, at least partly, in response to the stimulation of glutamate receptors. Two constitutive NOS isoforms are known: endothelial NOS (eNOS) and the neuronal isoform in the brain (nNOS) [18,19]. A single stress episode can cause an acute increase in the density of nNOS-positive neurons in the amygdala [20], and nNOS has been shown to be expressed in the postsynaptic sites of excitatory synapses in the LA [21].…”

Section: Introductionmentioning

confidence: 99%

Different Isoforms of Nitric Oxide Synthase Are Involved in Angiotensin-(1–7)-Mediated Plasticity Changes in the Amygdala in a Gender-Dependent Manner

Staschewski¹,

Kulisch²,

Albrecht³

2011

Neuroendocrinology

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Background: The amygdala receives afferent sensory input and processes information related to hydromineral balance. Angiotensin acts on and through the amygdala to stimulate thirst and sodium appetite. In addition, different angiotensins seem to play a role in cognition and learning mechanisms by acting on and through the amygdala. Recently, we showed that angiotensin-(1–7) (Ang-(1–7)) enhances the magnitude of long-term potentiation (LTP) in the lateral nucleus of the amygdala (LA) via the Mas receptor. Methods: Extracellular field potentials were measured in the LA. Results: LA-LTP induced by stimulation of the external capsule was nitric oxide (NO)-dependent because the NO synthase (NOS) inhibitor L-NAME reduced LA-LTP. The LA-LTP was also reduced in both male and female nNOS and eNOS knockout mice. In male eNOS^–/– mice, Ang-(1–7) enhanced LA-LTP, whereas the LTP-enhancing effect of Ang-(1–7) was missing in female eNOS^–/– mice. Therefore, the LTP-enhancing effect of Ang-(1–7) was mediated by eNOS in females. In contrast, Ang-(1–7) strongly enhanced the LTP in nNOS^–/– females, whereas the effect of Ang-(1–7) was missing in nNOS^–/– males. Thus, Ang-(1–7) induced an increase in the magnitude of LTP via the involvement of nNOS in males. Conclusion: Our data support not only the hypothesis that NO contributes to plasticity changes in the lateral amygdala, but also show for the first time a gender-dependent involvement of different isoforms of NOS in the mediation of Ang-(1–7) on LTP in the amygdala.

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Nitric Oxide Synthase Activity in Brain Regions and Spinal Cord of Mice and Rats: Kinetic Analysis

Cited by 47 publications

References 24 publications

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Core and Penumbral Nitric Oxide Synthase Activity During Cerebral Ischemia and Reperfusion

Different Isoforms of Nitric Oxide Synthase Are Involved in Angiotensin-(1–7)-Mediated Plasticity Changes in the Amygdala in a Gender-Dependent Manner

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