Region-specific alterations of neuronal nitric oxide synthase (nNOS) expression in the amygdala of the aged rats

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

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Neuronal nitric oxide synthase (nNOS) expression in the epithelial neuroendocrine cell system and nerve fibers in the gill of the catfish, Heteropneustes fossilis

Acta Histochemica ◽

10.1016/s0065-1281(99)80044-0 ◽

1999 ◽

Vol 101 (4) ◽

pp. 437-448 ◽

Cited By ~ 36

Author(s):

Angela Mauceri ◽

Salvatore Fasulo ◽

Luigi Ainis ◽

Aurelio Licata ◽

Eugenia Rita lauriano ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Cell System ◽

Nerve Fibers ◽

Neuroendocrine Cell ◽

Heteropneustes Fossilis ◽

Oxide Synthase ◽

Nnos Expression

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Decrease of neuronal nitric oxide synthase in the cerebellum of aged rats

Neuroscience Letters ◽

10.1016/s0304-3940(00)01377-x ◽

2000 ◽

Vol 291 (1) ◽

pp. 37-40 ◽

Cited By ~ 21

Author(s):

Wen-Jen Yu ◽

Shiow-Wen Juang ◽

Jie-Jen Lee ◽

Tsang-Pai Liu ◽

Juei-Tang Cheng

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Aged Rats ◽

Oxide Synthase

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Role of Sex Hormones and Their Receptors on Gastric Nrf2 and Neuronal Nitric Oxide Synthase Function in an Experimental Hyperglycemia Model

10.21203/rs.2.14913/v3 ◽

2020 ◽

Author(s):

Jeremy Sprouse ◽

Chethan Sampath ◽

PANDU GANGULA

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Sex Hormones ◽

Hormone Receptors ◽

Neuronal Nitric Oxide Synthase ◽

Nitrite Production ◽

Oxide Synthase ◽

Nnos Expression

Abstract Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

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Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00467.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R851-R857 ◽

Cited By ~ 19

Author(s):

Xavier Gamé ◽

Julien Allard ◽

Ghislaine Escourrou ◽

Pierre Gourdy ◽

Ivan Tack ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Structural Changes ◽

Neuronal Nitric Oxide Synthase ◽

Local Inhibition ◽

Ovariectomized Mice ◽

And Function ◽

Oxide Synthase ◽

Nnos Expression

Estrogens are known to modulate lower urinary tract (LUT) trophicity and neuronal nitric oxide synthase (nNOS) expression in several organs. The aim of this study was to explore the effects of endogenous and supraestrus levels of 17β-estradiol (E2) on LUT and urethral nNOS expression and function. LUT function and histology and urethral nNOS expression were studied in adult female mice subjected either to sham surgery, surgical castration, or castration plus chronic E2 supplementation (80 μg·kg−1·day−1, i.e., pregnancy level). The micturition pattern was profoundly altered by long-term supraestrus levels of E2 with decreased frequency paralleled by increased residual volumes higher than those of ovariectomized mice. Urethral resistance was increased twofold in E2-treated mice, with no structural changes in urethra, supporting a pure tonic mechanism. Acute nNOS inhibition by 7-nitroindazole decreased frequency and increased residual volumes in ovariectomized mice but had no additive effect on the micturition pattern of long-term supraestrus mice, showing that long-term supraestrus E2 levels and acute inhibition of nNOS activity had similar functional effects. Finally, E2 decreased urethral nNOS expression in ovariectomized mice. Long-term supraestrus levels of E2 increased urethral tone through inhibition of nNOS expression, whereas physiological levels of E2 had no effect.

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Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model

BMC Gastroenterology ◽

10.1186/s12876-020-01453-2 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jeremy Sprouse ◽

Chethan Sampath ◽

Pandu R. Gangula

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Sex Hormones ◽

Hormone Receptors ◽

Neuronal Nitric Oxide Synthase ◽

Nitrite Production ◽

Oxide Synthase ◽

Nnos Expression

Abstract Background Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods Gastric neuromuscular sections from adult female C57BL/6 J mice were incubated in normoglycemic (NG, 5 mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 h. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p < 0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

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