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The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder

Year 2016, Volume: 29 Issue: 2, 67 - 72, 01.04.2016

Beycan Gözde Ayhan Aslı Aykaç Kutlay Gür Banu Aydın Ece Seçgin İrem Seven Hülya Cabadak M Zafer Gören

https://doi.org/10.5472/MMJoa.2902.01
Cited By: 1

Abstract

Objectives: Activation of neuronal nitric oxide synthase (nNOS) and interrelated alterations of calmodulin and ionotropic glutamate receptor (GluN1) levels are unknown in post traumatic stress disorder (PTSD).Materials and Methods: Sprague-Dawley rats of both sexes were exposed to to dirty cat litter, and then placed on an elevated plus maze. An anxiety index was calculated and tissue samples from hippocampus and amygdala were prepered in order to detect calmodulin, NOS and GluN1 by immunoblotting.Results: The anxiety indices of the traumatized rats were markedly higher than those of the controls (p<0.05). GluN1 and calmodulin levels were decreased in the dorsal hippocampus and amygdaloid complex of the traumatized rats. NOS expression increased significantly in both the amygdaloid complex and dorsal hippocampus where the increase was statistically more prominent in the amygdaloid complex (p< 0.001) than in the dorsal hippocampus of the traumatized rats (p<0.05).Conclusion: Predator exposure in rats causes long-lasting anxiogenic effects associated with increases in NOS and decreases in GluN1 expressions in brain areas related to PTSD symptoms and excitotoxicity. The results suggest that excitotoxicity occurs through other mechanisms rather than GluN1 receptors.Keywords: Predator scent

References

  • Yehuda R. Risk and resilience in posttraumatic stress disorder. J Clinic Psychiatr 2004;65:26-36.
  • Griffin GD, Charron D, Al-Daccak R. Post-traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis. Clin Transl Immunology 2014;3:e27. doi: 10.1038/cti.2014.26
  • Zoladz PR, Diamond DM. Current status on behavioral and biological markers of PTSD: a search for clarity in a
  • conflicting literature Neurosci Biobehav Rev 2013;27:860-95. doi: 10.1016/j.neubiorev.2013.03.024
  • Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52:1048-60. doi:10.1001/archpsyc.1995.03950240066012.
  • Nemeroff CB, Bremner JD, Foa EB, Mayberg HS, North CS, Stein MB. Posttraumatic stress disorder: a state-of-thescience review. J Psychiatr Res 2005;40:1-21. doi: 10.1016/j.jpsychires.2005.07.005
  • Yehuda R, LeDoux J. Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 207;56: 19-32. doi:10.1016/j.neuron.2007.09.006
  • Andero R, Ressler KJ. Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes Brain Behav 2012;11:503-12. doi: 10.1111/j.1601-183X.2012.00801.x
  • Cohen, H., Zohar, J. An animal model of posttraumatic stress disorder: the use of cut-off behavioral criteria. Ann N Y Acad Sci 2004;1032:167-78. doi: 10.1196/annals.1314.014
  • Adamec R, Muir C, Grimes M, Pearcey K. Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress. Behav Brain Res 2007;179: 192-207. doi:10.1016/j.bbr.2007.02.001
  • Cohen H, Kaplan Z, Matar MA, Loewenthal U, Zohar J, Richter-Levin G. Long-lasting behavioral effects of juvenile trauma in an animal model of PTSD associated with a failure of the autonomic nervous system to recover. Eur Neuropsychopharmacol 2006;17:464-77. doi:10.1016/j.euroneuro.2006.11.003
  • Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human
  • neuroimaging research – past, present, and future. Biological Psychiatry 2006;60:376–82. doi:10.1016/j.biopsych.2006.06.004
  • Shin LM, Rauch SL, Pitman RK. Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann NY Acad Sci 2006;1071:67-79. doi: 10.1196/annals.1364.007
  • Bredt DS. Endogenous nitric oxide synthesis: biological functions and pathophysiology, Free Radic Res 1999;31 577–96. doi:10.1080/10715769900301161
  • Zhou L, Zhu DY. Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications. Nitric Oxide 2009;4:223-30. doi: 10.1016/j.niox.2009.03.001.
  • Vincent SR, Kimura H. Histochemical mapping of nitric oxide synthases in the rat brain. Neuroscience 1992;46:755–84. doi:10.1016/0306-4522(92)90184-4
  • Esplugues JV. NO as a signalling molecule in the nervous system. Br J Pharmacol 2002;135:1079-95. doi: 10.1038/sj.bjp.0704569
  • PrastH, Philippu A. Nitric oxide as modulator of neuronal function. Progress in Neurobiology 2001;64:51–68.
  • doi:10.1016/S0301-0082(00)00044-7
  • Padovan CM, Guimarães FS. Restraint-induced hypoactivity in an elevated plus-maze. Braz J Med Biol Res 2000;33:79–83.
  • Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 78 1994;78: 915-8. doi:10.1016/0092-8674(94)90266-6
  • Li H, Poulos TL. Structure-function studies on nitric oxide synthases, J Inorg Biochem 2005;99:293–305. doi:10.1016/j.jinorgbio.2004.10.016
  • Yamamoto Y, Katsumata O, Furuyama S, Sugiya H. Ca2+, calmodulin and phospholipids regulate nitric oxide synthase activity in the rabbit submandibular gland. J Comp Physiol
  • 174: 593-9. doi: 10.1007/s00360-004-0448-y
  • Courtney MJ, Nicholls DG. Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses. J Neurochem 1992;59:983-92. doi: 10.1111/j.1471-4159.1992.tb08339.x
  • Eichenbaum H. Acortical–hippocampal system for declarative memory. Nat Rev Neuroscience 2000;1:41-50.
  • doi:10.1038/35036213
  • Aggleton JP. The Amygdala A Functional Analysis. Oxford, UK: Oxford University Press, 2000: 213-87.
  • De Oliveira RW, Del Bel EA, Guimarães FS. Behavioral and c-fos expression changes induced by nitric oxide donors microinjected into the dorsal periaque- ductal gray. Brain Res Bull 2000;51:457-64. doi:10.1016/S0361-9230(99)00248-8
  • De Oliveira RW, Forestiero D, Manfrim CM, Guimarães FS. Anxiolytic effect induced by nitric oxide synthase
  • inhibitors microinjected at medial amygdala of rats. Eur Neuropsychopharm 2004;14(Suppl. 3):S316. doi:10.1016/
  • S0924-977X(04)80409-7
  • Masood A, Banerjee B, Vijauan VK, Ray A. Modulation of stress-induced neurobehavioural changes by nitric oxide in rats. Eur J Pharmacol 2003;458:135-9. doi:10.1016/S0014-2999(02)02688-2
  • Oliveira RW, Del Bel EA, Guimarães FS. Effects of excitatory amino acids and nitric oxide on flight behavior elicited from dorsolateral periaqueductal gray. Neurosci Biobehav Rev 2001:679-85. doi:10.1016/S0149-7634(01)00050-1
  • De Oliveira RW, Del Bel EA, Mamede-Rosa ML, Padovan CM, Deakin JF, Guimarães FS. Expression of neuronal nitric oxide synthase mRNA in stress-related brain areas after restraint stress. Neuroscience Letters 2000; 289:123-6. doi:10.1016/S0304-3940(00)01287-8

The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder

Year 2016, Volume: 29 Issue: 2, 67 - 72, 01.04.2016

Beycan Gözde Ayhan Aslı Aykaç Kutlay Gür Banu Aydın Ece Seçgin İrem Seven Hülya Cabadak M Zafer Gören

https://doi.org/10.5472/MMJoa.2902.01
Cited By: 1

Abstract

Objectives: Activation of neuronal nitric oxide synthase (nNOS) and interrelated alterations of calmodulin and ionotropic glutamate receptor (GluN1) levels are unknown in post traumatic stress disorder (PTSD).Materials and Methods: Sprague-Dawley rats of both sexes were exposed to to dirty cat litter, and then placed on an elevated plus maze. An anxiety index was calculated and tissue samples from hippocampus and amygdala were prepered in order to detect calmodulin, NOS and GluN1 by immunoblotting.Results: The anxiety indices of the traumatized rats were markedly higher than those of the controls (p<0.05). GluN1 and calmodulin levels were decreased in the dorsal hippocampus and amygdaloid complex of the traumatized rats. NOS expression increased significantly in both the amygdaloid complex and dorsal hippocampus where the increase was statistically more prominent in the amygdaloid complex (p< 0.001) than in the dorsal hippocampus of the traumatized rats (p<0.05).Conclusion: Predator exposure in rats causes long-lasting anxiogenic effects associated with increases in NOS and decreases in GluN1 expressions in brain areas related to PTSD symptoms and excitotoxicity. The results suggest that excitotoxicity occurs through other mechanisms rather than GluN1 receptors.Keywords: Predator scent

Keywords

Saldırgan hayvan kokusu testi nNOS

References

  • Yehuda R. Risk and resilience in posttraumatic stress disorder. J Clinic Psychiatr 2004;65:26-36.
  • Griffin GD, Charron D, Al-Daccak R. Post-traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis. Clin Transl Immunology 2014;3:e27. doi: 10.1038/cti.2014.26
  • Zoladz PR, Diamond DM. Current status on behavioral and biological markers of PTSD: a search for clarity in a
  • conflicting literature Neurosci Biobehav Rev 2013;27:860-95. doi: 10.1016/j.neubiorev.2013.03.024
  • Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52:1048-60. doi:10.1001/archpsyc.1995.03950240066012.
  • Nemeroff CB, Bremner JD, Foa EB, Mayberg HS, North CS, Stein MB. Posttraumatic stress disorder: a state-of-thescience review. J Psychiatr Res 2005;40:1-21. doi: 10.1016/j.jpsychires.2005.07.005
  • Yehuda R, LeDoux J. Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 207;56: 19-32. doi:10.1016/j.neuron.2007.09.006
  • Andero R, Ressler KJ. Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes Brain Behav 2012;11:503-12. doi: 10.1111/j.1601-183X.2012.00801.x
  • Cohen, H., Zohar, J. An animal model of posttraumatic stress disorder: the use of cut-off behavioral criteria. Ann N Y Acad Sci 2004;1032:167-78. doi: 10.1196/annals.1314.014
  • Adamec R, Muir C, Grimes M, Pearcey K. Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress. Behav Brain Res 2007;179: 192-207. doi:10.1016/j.bbr.2007.02.001
  • Cohen H, Kaplan Z, Matar MA, Loewenthal U, Zohar J, Richter-Levin G. Long-lasting behavioral effects of juvenile trauma in an animal model of PTSD associated with a failure of the autonomic nervous system to recover. Eur Neuropsychopharmacol 2006;17:464-77. doi:10.1016/j.euroneuro.2006.11.003
  • Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human
  • neuroimaging research – past, present, and future. Biological Psychiatry 2006;60:376–82. doi:10.1016/j.biopsych.2006.06.004
  • Shin LM, Rauch SL, Pitman RK. Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann NY Acad Sci 2006;1071:67-79. doi: 10.1196/annals.1364.007
  • Bredt DS. Endogenous nitric oxide synthesis: biological functions and pathophysiology, Free Radic Res 1999;31 577–96. doi:10.1080/10715769900301161
  • Zhou L, Zhu DY. Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications. Nitric Oxide 2009;4:223-30. doi: 10.1016/j.niox.2009.03.001.
  • Vincent SR, Kimura H. Histochemical mapping of nitric oxide synthases in the rat brain. Neuroscience 1992;46:755–84. doi:10.1016/0306-4522(92)90184-4
  • Esplugues JV. NO as a signalling molecule in the nervous system. Br J Pharmacol 2002;135:1079-95. doi: 10.1038/sj.bjp.0704569
  • PrastH, Philippu A. Nitric oxide as modulator of neuronal function. Progress in Neurobiology 2001;64:51–68.
  • doi:10.1016/S0301-0082(00)00044-7
  • Padovan CM, Guimarães FS. Restraint-induced hypoactivity in an elevated plus-maze. Braz J Med Biol Res 2000;33:79–83.
  • Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 78 1994;78: 915-8. doi:10.1016/0092-8674(94)90266-6
  • Li H, Poulos TL. Structure-function studies on nitric oxide synthases, J Inorg Biochem 2005;99:293–305. doi:10.1016/j.jinorgbio.2004.10.016
  • Yamamoto Y, Katsumata O, Furuyama S, Sugiya H. Ca2+, calmodulin and phospholipids regulate nitric oxide synthase activity in the rabbit submandibular gland. J Comp Physiol
  • 174: 593-9. doi: 10.1007/s00360-004-0448-y
  • Courtney MJ, Nicholls DG. Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses. J Neurochem 1992;59:983-92. doi: 10.1111/j.1471-4159.1992.tb08339.x
  • Eichenbaum H. Acortical–hippocampal system for declarative memory. Nat Rev Neuroscience 2000;1:41-50.
  • doi:10.1038/35036213
  • Aggleton JP. The Amygdala A Functional Analysis. Oxford, UK: Oxford University Press, 2000: 213-87.
  • De Oliveira RW, Del Bel EA, Guimarães FS. Behavioral and c-fos expression changes induced by nitric oxide donors microinjected into the dorsal periaque- ductal gray. Brain Res Bull 2000;51:457-64. doi:10.1016/S0361-9230(99)00248-8
  • De Oliveira RW, Forestiero D, Manfrim CM, Guimarães FS. Anxiolytic effect induced by nitric oxide synthase
  • inhibitors microinjected at medial amygdala of rats. Eur Neuropsychopharm 2004;14(Suppl. 3):S316. doi:10.1016/
  • S0924-977X(04)80409-7
  • Masood A, Banerjee B, Vijauan VK, Ray A. Modulation of stress-induced neurobehavioural changes by nitric oxide in rats. Eur J Pharmacol 2003;458:135-9. doi:10.1016/S0014-2999(02)02688-2
  • Oliveira RW, Del Bel EA, Guimarães FS. Effects of excitatory amino acids and nitric oxide on flight behavior elicited from dorsolateral periaqueductal gray. Neurosci Biobehav Rev 2001:679-85. doi:10.1016/S0149-7634(01)00050-1
  • De Oliveira RW, Del Bel EA, Mamede-Rosa ML, Padovan CM, Deakin JF, Guimarães FS. Expression of neuronal nitric oxide synthase mRNA in stress-related brain areas after restraint stress. Neuroscience Letters 2000; 289:123-6. doi:10.1016/S0304-3940(00)01287-8
There are 36 citations in total.

Details

Subjects Clinical Sciences
Other ID JA54AD78FA
Journal Section Review Makaleler
Authors

Beycan Gözde Ayhan This is me

Aslı Aykaç This is me

Kutlay Gür This is me

Banu Aydın This is me

Ece Seçgin This is me

İrem Seven This is me

Hülya Cabadak This is me

M Zafer Gören This is me

Publication Date April 1, 2016
Published in Issue Year 2016 Volume: 29 Issue: 2

Cite

APA Ayhan, B. G., Aykaç, A., Gür, K., Aydın, B., et al. (2016). The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder. Marmara Medical Journal, 29(2), 67-72. https://doi.org/10.5472/MMJoa.2902.01
AMA Ayhan BG, Aykaç A, Gür K, Aydın B, Seçgin E, Seven İ, Cabadak H, Gören MZ. The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder. Marmara Med J. April 2016;29(2):67-72. doi:10.5472/MMJoa.2902.01
Chicago Ayhan, Beycan Gözde, Aslı Aykaç, Kutlay Gür, Banu Aydın, Ece Seçgin, İrem Seven, Hülya Cabadak, and M Zafer Gören. “The Role of GluN1 Activated Nitric Oxide Synthase in a Rat Model of Post-Traumatic Stress Disorder”. Marmara Medical Journal 29, no. 2 (April 2016): 67-72. https://doi.org/10.5472/MMJoa.2902.01.
EndNote Ayhan BG, Aykaç A, Gür K, Aydın B, Seçgin E, Seven İ, Cabadak H, Gören MZ (April 1, 2016) The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder. Marmara Medical Journal 29 2 67–72.
IEEE B. G. Ayhan, A. Aykaç, K. Gür, B. Aydın, E. Seçgin, İ. Seven, H. Cabadak, and M. Z. Gören, “The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder”, Marmara Med J, vol. 29, no. 2, pp. 67–72, 2016, doi: 10.5472/MMJoa.2902.01.
ISNAD Ayhan, Beycan Gözde et al. “The Role of GluN1 Activated Nitric Oxide Synthase in a Rat Model of Post-Traumatic Stress Disorder”. Marmara Medical Journal 29/2 (April 2016), 67-72. https://doi.org/10.5472/MMJoa.2902.01.
JAMA Ayhan BG, Aykaç A, Gür K, Aydın B, Seçgin E, Seven İ, Cabadak H, Gören MZ. The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder. Marmara Med J. 2016;29:67–72.
MLA Ayhan, Beycan Gözde et al. “The Role of GluN1 Activated Nitric Oxide Synthase in a Rat Model of Post-Traumatic Stress Disorder”. Marmara Medical Journal, vol. 29, no. 2, 2016, pp. 67-72, doi:10.5472/MMJoa.2902.01.
Vancouver Ayhan BG, Aykaç A, Gür K, Aydın B, Seçgin E, Seven İ, Cabadak H, Gören MZ. The role of GluN1 activated nitric oxide synthase in a rat model of post-traumatic stress disorder. Marmara Med J. 2016;29(2):67-72.

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