A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats.
Depression is a common stress disability disorder that affects higher mental functions including emotion, cognition, and behavior. It may be mediated by inflammatory cytokines that interfere with neuroendocrine function, and synaptic plasticity. Therefore, reductions in inflammation might contribute...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0296187 |
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| author | Ghida Hassan Sherif A Kamar Hagar Yousry Rady Dina Sayed Abdelrahim Nesma Hussein Abdel Hay Ibrahim Noha N Lasheen |
| author_facet | Ghida Hassan Sherif A Kamar Hagar Yousry Rady Dina Sayed Abdelrahim Nesma Hussein Abdel Hay Ibrahim Noha N Lasheen |
| author_sort | Ghida Hassan |
| collection | DOAJ |
| description | Depression is a common stress disability disorder that affects higher mental functions including emotion, cognition, and behavior. It may be mediated by inflammatory cytokines that interfere with neuroendocrine function, and synaptic plasticity. Therefore, reductions in inflammation might contribute to treatment response. The current study aims to evaluate the role of Protein Kinase (PKA)- cAMP response element-binding protein (CREB)- brain derived neurotropic factor (BDNF) signaling pathway in depression and the effects of roflumilast (PDE4 inhibitor) as potential antidepressant on the activity of the PKA-CREB-BDNF signaling pathway, histology, and pro-inflammatory cytokine production. Forty Adult male Wistar rats were divided into 4 groups: Control group, Positive Control group: similar to the controls but received Roflumilast (3 mg / kg / day) by oral gavage for the last 4 weeks of the experiment, Depressed group which were exposed to chronic stress for 6 weeks, and Roflumilast-treated group which were exposed to chronic stress for 6 weeks and treated by Roflumilast (3 mg / kg / day) by oral gavage for the last 4 weeks of the experiment. The depressed group showed significant increase in immobility time with significant decrease in swimming and struggling times, significant decrease in hippocampal PKA, CERB, BDNF, Dopamine, Cortisone, and Superoxide dismutase while hippocampal Phosphodiesterase-E4, Interleukin-6, and Malondialdhyde levels were significantly elevated. These findings were significantly reversed upon Roflumilast treatment. Therefore, it could be concluded that depression is a neurodegenerative inflammatory disease and oxidative stress plays a key role in depression. Roflumilast treatment attenuated the depression behavior in rats denoting its neuroprotective, and anti-inflammatory effects. |
| first_indexed | 2024-03-08T05:11:53Z |
| format | Article |
| id | doaj.art-2b3ceea92594484ba8fa3824affa1c09 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T05:11:53Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2b3ceea92594484ba8fa3824affa1c092024-02-07T05:31:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01192e029618710.1371/journal.pone.0296187A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats.Ghida HassanSherif A KamarHagar Yousry RadyDina Sayed AbdelrahimNesma Hussein Abdel Hay IbrahimNoha N LasheenDepression is a common stress disability disorder that affects higher mental functions including emotion, cognition, and behavior. It may be mediated by inflammatory cytokines that interfere with neuroendocrine function, and synaptic plasticity. Therefore, reductions in inflammation might contribute to treatment response. The current study aims to evaluate the role of Protein Kinase (PKA)- cAMP response element-binding protein (CREB)- brain derived neurotropic factor (BDNF) signaling pathway in depression and the effects of roflumilast (PDE4 inhibitor) as potential antidepressant on the activity of the PKA-CREB-BDNF signaling pathway, histology, and pro-inflammatory cytokine production. Forty Adult male Wistar rats were divided into 4 groups: Control group, Positive Control group: similar to the controls but received Roflumilast (3 mg / kg / day) by oral gavage for the last 4 weeks of the experiment, Depressed group which were exposed to chronic stress for 6 weeks, and Roflumilast-treated group which were exposed to chronic stress for 6 weeks and treated by Roflumilast (3 mg / kg / day) by oral gavage for the last 4 weeks of the experiment. The depressed group showed significant increase in immobility time with significant decrease in swimming and struggling times, significant decrease in hippocampal PKA, CERB, BDNF, Dopamine, Cortisone, and Superoxide dismutase while hippocampal Phosphodiesterase-E4, Interleukin-6, and Malondialdhyde levels were significantly elevated. These findings were significantly reversed upon Roflumilast treatment. Therefore, it could be concluded that depression is a neurodegenerative inflammatory disease and oxidative stress plays a key role in depression. Roflumilast treatment attenuated the depression behavior in rats denoting its neuroprotective, and anti-inflammatory effects.https://doi.org/10.1371/journal.pone.0296187 |
| spellingShingle | Ghida Hassan Sherif A Kamar Hagar Yousry Rady Dina Sayed Abdelrahim Nesma Hussein Abdel Hay Ibrahim Noha N Lasheen A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats. PLoS ONE |
| title | A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats. |
| title_full | A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats. |
| title_fullStr | A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats. |
| title_full_unstemmed | A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats. |
| title_short | A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats. |
| title_sort | study of roflumilast treatment on functional and structural changes in hippocampus in depressed adult male wistar rats |
| url | https://doi.org/10.1371/journal.pone.0296187 |
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