Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine
Despite several antidepressant treatments being available in clinics, they are not effective in all patients. In recent years, N-acetylcysteine (NAC) has been explored as adjunctive therapy for many psychiatric disorders, including depression, for its antioxidant properties. Given the promising effi...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7321 |
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| author | Paola Brivio Maria Teresa Gallo Piotr Gruca Magdalena Lason Ewa Litwa Fabio Fumagalli Mariusz Papp Francesca Calabrese |
| author_facet | Paola Brivio Maria Teresa Gallo Piotr Gruca Magdalena Lason Ewa Litwa Fabio Fumagalli Mariusz Papp Francesca Calabrese |
| author_sort | Paola Brivio |
| collection | DOAJ |
| description | Despite several antidepressant treatments being available in clinics, they are not effective in all patients. In recent years, N-acetylcysteine (NAC) has been explored as adjunctive therapy for many psychiatric disorders, including depression, for its antioxidant properties. Given the promising efficacy of this compound for the treatment of such pathologies, it is fundamental to investigate, at the preclinical level, the ability of the drug to act in the modulation of neuroplastic mechanisms in basal conditions and during challenging events in order to highlight the potential features of the drug useful for clinical efficacy. To this aim, adult male Wistar rats were treated with the antidepressant venlafaxine (VLX) (10 mg/kg) or NAC (300 mg/kg) for 21 days and then subjected to 1 h of acute restraint stress (ARS). We found that NAC enhanced the expression of several immediate early genes, markers of neuronal plasticity in the ventral and dorsal hippocampus, prefrontal cortex and amygdala, and in particular it mediated the acute-stress-induced upregulation of <i>Nr4a1</i> expression more than VLX. These data suggested the ability of NAC to induce coping strategies to face external challenges, highlighting its potential for the improvement of neuroplastic mechanisms for the promotion of resilience, in particular via the modulation of <i>Nr4a1</i>. |
| first_indexed | 2024-03-11T04:55:58Z |
| format | Article |
| id | doaj.art-46e2837e5e374d07a1e9419eb0f77352 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:55:58Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-46e2837e5e374d07a1e9419eb0f773522023-11-17T19:38:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248732110.3390/ijms24087321Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant VenlafaxinePaola Brivio0Maria Teresa Gallo1Piotr Gruca2Magdalena Lason3Ewa Litwa4Fabio Fumagalli5Mariusz Papp6Francesca Calabrese7Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milan, ItalyMaj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, PolandMaj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, PolandMaj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, PolandDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milan, ItalyMaj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, PolandDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milan, ItalyDespite several antidepressant treatments being available in clinics, they are not effective in all patients. In recent years, N-acetylcysteine (NAC) has been explored as adjunctive therapy for many psychiatric disorders, including depression, for its antioxidant properties. Given the promising efficacy of this compound for the treatment of such pathologies, it is fundamental to investigate, at the preclinical level, the ability of the drug to act in the modulation of neuroplastic mechanisms in basal conditions and during challenging events in order to highlight the potential features of the drug useful for clinical efficacy. To this aim, adult male Wistar rats were treated with the antidepressant venlafaxine (VLX) (10 mg/kg) or NAC (300 mg/kg) for 21 days and then subjected to 1 h of acute restraint stress (ARS). We found that NAC enhanced the expression of several immediate early genes, markers of neuronal plasticity in the ventral and dorsal hippocampus, prefrontal cortex and amygdala, and in particular it mediated the acute-stress-induced upregulation of <i>Nr4a1</i> expression more than VLX. These data suggested the ability of NAC to induce coping strategies to face external challenges, highlighting its potential for the improvement of neuroplastic mechanisms for the promotion of resilience, in particular via the modulation of <i>Nr4a1</i>.https://www.mdpi.com/1422-0067/24/8/7321restraintantioxidantIEGsneuroplastic mechanismsratspsychiatric disorders |
| spellingShingle | Paola Brivio Maria Teresa Gallo Piotr Gruca Magdalena Lason Ewa Litwa Fabio Fumagalli Mariusz Papp Francesca Calabrese Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine International Journal of Molecular Sciences restraint antioxidant IEGs neuroplastic mechanisms rats psychiatric disorders |
| title | Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine |
| title_full | Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine |
| title_fullStr | Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine |
| title_full_unstemmed | Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine |
| title_short | Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene <i>Nr4a1</i> in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine |
| title_sort | chronic n acetyl cysteine treatment enhances the expression of the immediate early gene i nr4a1 i in response to an acute challenge in male rats comparison with the antidepressant venlafaxine |
| topic | restraint antioxidant IEGs neuroplastic mechanisms rats psychiatric disorders |
| url | https://www.mdpi.com/1422-0067/24/8/7321 |
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