{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T12:56:44Z","timestamp":1773752204882,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["2\/0118\/21"],"award-info":[{"award-number":["2\/0118\/21"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Social isolation deprives rodents of social interactions that are critical for normal development of brain and behavior. Several studies have indicated that postweaning isolation rearing may affect nitric oxide (NO) production. The aim of this study was to compare selected behavioral and biochemical changes related to NO production in the brain of rats reared in social isolation for different duration. At the age of 21 days, male Sprague Dawley rats were randomly assigned into four groups reared in isolation or socially for 10 or 29 weeks. At the end of the rearing, open-field and prepulse inhibition (PPI) tests were carried out. Furthermore, in several brain areas we assessed NO synthase (NOS) activity, protein expression of nNOS and iNOS isoforms and the concentration of conjugated dienes (CD), a marker of oxidative damage and lipid peroxidation. Social isolation for 10 weeks resulted in a significant decrease in PPI, which was accompanied by a decrease in NOS activity in the cerebral cortex and the cerebellum, an increase in iNOS in the hippocampus and an increase in CD concentration in cortex homogenate. On the other hand, a 29 week isolation had an opposite effect on NOS activity, which increased in the cerebral cortex and the cerebellum in animals reared in social isolation, accompanied by a decrease in CD concentration. The decrease in NOS activity after 10 weeks of isolation might have been caused by chronic stress induced by social isolation, which has been documented in previous studies. The increased oxidative state might result in the depleted NO bioavailability, as NO reacts with superoxide radical creating peroxynitrite. After 29 weeks of isolation, this loss of NO might be compensated by the subsequent increase in NOS activity.<\/jats:p>","DOI":"10.3390\/ijms221910340","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T04:55:33Z","timestamp":1632718533000},"page":"10340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Duration of Social Isolation Affects Production of Nitric Oxide in the Rat Brain"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9183-4275","authenticated-orcid":false,"given":"Stanislava","family":"Vrankova","sequence":"first","affiliation":[{"name":"Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzana","family":"Galandakova","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-0287","authenticated-orcid":false,"given":"Jakub","family":"Benko","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-670X","authenticated-orcid":false,"given":"Martina","family":"Cebova","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4211-8993","authenticated-orcid":false,"given":"Igor","family":"Riecansky","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"},{"name":"Social, Cognitive and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, 1010 Vienna, Austria"},{"name":"Department of Psychiatry, Slovak Medical University, 833 03 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5476-2949","authenticated-orcid":false,"given":"Olga","family":"Pechanova","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1210\/en.2007-1469","article-title":"Early Life Stress Enhances the Vulnerability to Chronic Psychosocial Stress and Experimental Colitis in Adult Mice","volume":"149","author":"Veenema","year":"2008","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fnsyn.2014.00004","article-title":"The best-laid plans go oft awry: Synaptogenic growth factor signaling in neuropsychiatric disease","volume":"6","author":"Williams","year":"2014","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.biopha.2018.05.086","article-title":"Neurobiology and consequences of social isolation stress in animal model\u2014A comprehensive review","volume":"105","author":"Mumtaz","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuroscience.2008.12.019","article-title":"Effects of social isolation rearing on the limbic brain: A combined behavioral and magnetic resonance imaging volumetry study in rats","volume":"159","author":"Schubert","year":"2009","journal-title":"Neuroscience"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.neubiorev.2010.02.008","article-title":"Early life influences on emotional reactivity: Evidence that social enrichment has greater effects than handling on anxiety-like behaviors, neuroendocrine responses to stress and central BDNF levels","volume":"34","author":"Cirulli","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.bbr.2006.09.017","article-title":"Aggressive behavior and HPA axis hormones after social isolation in adult rats of two different genetic animal models for depression","volume":"175","author":"Malkesman","year":"2006","journal-title":"Behav. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bbi.2015.08.003","article-title":"Disruptions of sensorimotor gating, cytokines, glycemia, monoamines, and genes in both sexes of rats reared in social isolation can be ameliorated by oral chronic quetiapine administration","volume":"51","author":"Ko","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.brainres.2011.02.035","article-title":"Isolation rearing alters social behaviors and monoamine neurotransmission in the medial prefrontal cortex and nucleus accumbens of adult rats","volume":"1385","author":"Han","year":"2011","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.bbr.2015.01.005","article-title":"Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus","volume":"282","author":"Shao","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fnbeh.2017.00101","article-title":"The Evidence for Altered BDNF Expression in the Brain of Rats Reared or Housed in Social Isolation: A Systematic Review","volume":"11","year":"2017","journal-title":"Front. Behav. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.yhbeh.2011.02.003","article-title":"Post-weaning social isolation induces abnormal forms of aggression in conjunction with increased glucocorticoid and autonomic stress responses","volume":"60","author":"Toth","year":"2011","journal-title":"Horm. Behav."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.physbeh.2015.03.032","article-title":"Co-occurrence of anxiety and depressive-like behaviors following adolescent social isolation in male mice; possible role of nitrergic system","volume":"145","author":"Amiri","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/S0959-4388(97)80065-7","article-title":"Synaptic signaling by nitric oxide","volume":"7","author":"Brenman","year":"1997","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1083\/jcb.200805132","article-title":"PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling","volume":"183","author":"Nikonenko","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1073\/pnas.1218126110","article-title":"S-nitrosylation of HDAC2 regulates the expression of the chromatin-remodeling factor Brm during radial neuron migration","volume":"110","author":"Nott","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/0092-8674(93)90615-W","article-title":"Targeted disruption of the neuronal nitric oxide synthase gene","volume":"75","author":"Huang","year":"1993","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3389\/fncel.2013.00190","article-title":"The role of nitric oxide in pre-synaptic plasticity and homeostasis","volume":"7","author":"Hardingham","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.schres.2005.05.019","article-title":"The many faces of nitric oxide in schizophrenia. A review","volume":"78","author":"Bernstein","year":"2005","journal-title":"Schizophr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/1073858410366481","article-title":"Nitric Oxide Signaling in Brain Function, Dysfunction, and Dementia","volume":"16","author":"Steinert","year":"2010","journal-title":"Neuroscientist"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00441-018-02987-4","article-title":"Nitric oxide signalling and antidepressant action revisited","volume":"377","author":"Joca","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0006-8993(01)02613-0","article-title":"Neuronal and inducible nitric oxide synthase expression and protein nitration in rat cerebellum after oxygen and glucose deprivation","volume":"909","author":"Rodrigo","year":"2001","journal-title":"Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8071","DOI":"10.1007\/s12035-016-0297-1","article-title":"Inflammatory Response in the CNS: Friend or Foe?","volume":"54","author":"Sochocka","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1111\/j.1471-4159.2007.04914.x","article-title":"Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis","volume":"103","author":"Zhou","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000087555","article-title":"Morphological Abnormalities in Nitric-Oxide-Synthase-Positive Striatal Interneurons of Schizophrenic Patients","volume":"52","author":"Lauer","year":"2005","journal-title":"Neuropsychobiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3389\/fphys.2015.00139","article-title":"Role of nitric oxide and related molecules in schizophrenia pathogenesis: Biochemical, genetic and clinical aspects","volume":"6","author":"Nasyrova","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0031-9384(99)00082-7","article-title":"Ontogeny of Isolation Rearing-Induced Deficits in Sensorimotor Gating in Rats","volume":"67","author":"Bakshi","year":"1999","journal-title":"Physiol. Behav."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104473","DOI":"10.1016\/j.neuint.2019.104473","article-title":"Behavioral alterations induced by post-weaning isolation rearing of rats are accompanied by reduced VGF\/BDNF\/TrkB signaling in the hippocampus","volume":"129","author":"Chmelova","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ejphar.2004.09.042","article-title":"The neuronal selective nitric oxide synthase inhibitor, N\u03c9-propyl-l-arginine, blocks the effects of phencyclidine on prepulse inhibition and locomotor activity in mice","volume":"503","author":"Klamer","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1038\/sj.npp.1301587","article-title":"Nitric Oxide Signaling in the Medial Prefrontal Cortex is Involved in the Biochemical and Behavioral Effects of Phencyclidine","volume":"33","author":"Fejgin","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00213-013-3277-4","article-title":"Critical role of nitric oxide in the modulation of prepulse inhibition in Swiss mice","volume":"231","author":"Issy","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75e89","DOI":"10.1016\/j.mam.2004.02.010","article-title":"Nitric oxide in brain: Diffusion, targets and concentration dynamics in hippocampal subregions","volume":"25","author":"Ledo","year":"2004","journal-title":"Mol. Asp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1111\/j.1471-4159.2006.03988.x","article-title":"Nitric oxide, cell bioenergetics and neurodegeneration","volume":"97","author":"Moncada","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.bbr.2010.11.016","article-title":"Nitric oxide synthase inhibitors improve prepulse inhibition responses of Wistar rats","volume":"217","author":"Issy","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/0091-3057(93)90193-W","article-title":"Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia","volume":"44","author":"Swerdlow","year":"1993","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s002130100810","article-title":"Human studies of prepulse inhibition of startle: Normal subjects, patient groups, and pharmacological studies","volume":"156","author":"Braff","year":"2001","journal-title":"Psychopharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3389\/fncel.2019.00331","article-title":"Dopamine Receptor Blockade Attenuates Purinergic P2X4 Receptor-Mediated Prepulse Inhibition Deficits and Underlying Molecular Mechanisms","volume":"13","author":"Khoja","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1124\/jpet.104.074468","article-title":"Dopamine D1 and D2 Agonist Effects on Prepulse Inhibition and Locomotion: Comparison of Sprague-Dawley Rats to Swiss-Webster, 129X1\/SvJ, C57BL\/6J, and DBA\/2J Mice","volume":"312","author":"Ralph","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28139","DOI":"10.1074\/jbc.M003198200","article-title":"Inhibition of Neuronal Nitric-oxide Synthase by Calcium\/Calmodulin-dependent Protein Kinase II\u03b1 through Ser847 Phosphorylation in NG108-15 Neuronal Cells","volume":"275","author":"Komeima","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1756-6606-2-19","article-title":"Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice","volume":"2","author":"Tanda","year":"2009","journal-title":"Mol. Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.neuint.2013.06.002","article-title":"Chronic social isolation induces NF-\u03baB activation and upregulation of iNOS protein expression in rat prefrontal cortex","volume":"63","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00702-013-1066-1","article-title":"Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus","volume":"121","author":"Bernardi","year":"2014","journal-title":"J. Neural Transm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2174\/187152706778559327","article-title":"Stress-Induced Oxidative Changes in Brain","volume":"5","author":"Madrigal","year":"2006","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.neuroscience.2012.08.005","article-title":"Bax and B-cell-lymphoma 2 mediate proapoptotic signaling following chronic isolation stress in rat brain","volume":"223","year":"2012","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1002\/jnr.22687","article-title":"Chronic isolation stress predisposes the frontal cortex but not the hippocampus to the potentially detrimental release of cytochrome c from mitochondria and the activation of caspase-3","volume":"89","author":"Inta","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s12192-010-0226-6","article-title":"Increased stability of Bcl-2 in HSP70-mediated protection against apoptosis induced by oxidative stress","volume":"16","author":"Jiang","year":"2011","journal-title":"Cell Stress Chaperon"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/3-540-29717-0_8","article-title":"Heat Shock Proteins: Endogenous Modulators of Apoptotic Cell Death","volume":"26","author":"Didelot","year":"2006","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/pmic.200390065","article-title":"Stress protein flux during recovery from simulated ischemia: Induced heat shock protein 70 confers cytoprotection by suppressing JNK activation and inhibiting apoptotic cell death","volume":"3","author":"Kumar","year":"2003","journal-title":"Proteomics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/978-3-540-68964-5_24","article-title":"cGMP Signalling in the Mammalian Brain: Role in Synaptic Plasticity and Behaviour","volume":"191","author":"Kleppisch","year":"2009","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s12311-010-0234-1","article-title":"Role of Nitric Oxide in Cerebellar Development and Function: Focus on Granule Neurons","volume":"11","author":"Contestabile","year":"2012","journal-title":"Cerebellum"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1126\/science.2166337","article-title":"A family of AMPA-selective glutamate receptors","volume":"249","author":"Keinanen","year":"1990","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.neulet.2014.06.062","article-title":"Nitric oxide show its survival role by NO-PKC pathway through cGMP-dependent or independent on the culture of cerebella granular neurons","volume":"583","author":"Wang","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/j.1471-4159.2007.04811.x","article-title":"Frontal cortical afferents facilitate striatal nitric oxide transmission in vivo via a NMDA receptor and neuronal NOS-dependent mechanism","volume":"103","author":"Sammut","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1097\/01.ALC.0000145755.72834.F1","article-title":"Inhibition of nitric oxide release in vivo by ethanol","volume":"28","author":"Rossetti","year":"2004","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00213-009-1687-0","article-title":"Impact of dopamine\u2013glutamate interactions on striatal neuronal nitric oxide synthase activity","volume":"207","author":"Hoque","year":"2010","journal-title":"Psychopharmacology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1590\/S0100-879X2008001200001","article-title":"Stress-induced neuroinflammation: Mechanisms and new pharmacological targets","volume":"41","author":"Munhoz","year":"2008","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Shal, B., Khan, A., Khan, A., Ullah, R., Ali, G., Islam, S., Haq, I., Ali, H., Seo, E.-K., and Khan, S. (2021). Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2\/NF-\u03baB Pathway in Transgenic Mouse Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126603"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1089\/ars.2011.4406","article-title":"4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies","volume":"17","author":"Perluigi","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Khan, A., Shal, B., Khan, A., Ullah, R., Baig, M., Haq, I.U., Seo, E., and Khan, S. (2021). Suppression of TRPV1\/TRPM8\/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116084"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/sj.mp.4000789","article-title":"Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia","volume":"6","author":"Herken","year":"2001","journal-title":"Mol. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.schres.2005.10.011","article-title":"Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics","volume":"81","author":"Zhang","year":"2006","journal-title":"Schizophr. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s11011-013-9433-z","article-title":"N-acetyl cysteine reverses social isolation rearing induced changes in cortico-striatal monoamines in rats","volume":"28","author":"Viljoen","year":"2013","journal-title":"Metab. Brain Dis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Meza, C.A., La Favor, J.D., Kim, D.-H., and Hickner, R.C. (2019). Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153775"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.yhbeh.2008.02.004","article-title":"Chronic treatment with the mineralocorticoid hormone aldosterone results in increased anxiety-like behavior","volume":"54","author":"Hlavacova","year":"2008","journal-title":"Horm. Behav."},{"key":"ref_64","first-page":"7","article-title":"Measurement of Startle Response, Prepulse Inhibition, and Habituation","volume":"8","author":"Geyer","year":"2001","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1073\/pnas.87.2.682","article-title":"Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme","volume":"87","author":"Bredt","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1006\/jmcc.1997.0566","article-title":"Protein Remodelling of the Heart in NO-deficient Hypertension: The Effect of Captopril","volume":"29","author":"Pelouch","year":"1997","journal-title":"J. Mol. Cell. Cardiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:05:04Z","timestamp":1760166304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,25]]},"references-count":66,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910340"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910340","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,25]]}}}