Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors
Ischemia in the medial prefrontal cortex (mPFC) causes cognitive impairment in stroke cases. This study aimed to examine the effects of varenicline as α7 and α4β2 nicotine acetylcholine receptors (nAChRs) agonist, on cognitive impairment, inflammation, apoptosis, and synaptic dysfunction in mPFC isc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923022000144 |
| _version_ | 1827392001772879872 |
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| author | Fatemehsadat Seyedaghamiri Leila Hosseini Sareh Kazmi Javad Mahmoudi Dariush Shanehbandi Abbas Ebrahimi-Kalan Reza Rahbarghazi Saeed Sadigh-Eteghad Mehdi Farhoudi |
| author_facet | Fatemehsadat Seyedaghamiri Leila Hosseini Sareh Kazmi Javad Mahmoudi Dariush Shanehbandi Abbas Ebrahimi-Kalan Reza Rahbarghazi Saeed Sadigh-Eteghad Mehdi Farhoudi |
| author_sort | Fatemehsadat Seyedaghamiri |
| collection | DOAJ |
| description | Ischemia in the medial prefrontal cortex (mPFC) causes cognitive impairment in stroke cases. This study aimed to examine the effects of varenicline as α7 and α4β2 nicotine acetylcholine receptors (nAChRs) agonist, on cognitive impairment, inflammation, apoptosis, and synaptic dysfunction in mPFC ischemia. Mice were divided to three groups of control, sham, or photothrombotic mPFC ischemia model. The control and sham groups received 2 ml/kg of normal saline for a 14-day period. As well, the animals in the ischemia groups received normal saline (2 ml/kg) or varenicline at 0.1, 1, and 3 mg/kg doses for a 14-day period. Anxiety-like behaviors were then assessed by open field (OFT) and elevated plus-maze (EPM) tests. Memory was also evaluated using Morris water maze (MWM) and novel object recognition (NOR) tests. The levels of inflammatory (IL-1β, TNF-α), apoptotic (Bax, caspase3, BCL-2), and synaptic (SYP, PSD-95, and GAP-43) proteins were examined using the western blot method. In addition, the histological evaluation was performed to assess tissue damage. The administration of Varenicline at the dose of 3 mg/kg reduced the IL-1β, TNF-α, Bax, and caspase3 levels. Moreover, it increased BCL-2, SYP, PSD-95, and GAP-43 levels at the same dose and ameliorated memory impairment and anxiety-like behaviors in mPFC ischemic mice. Varenicline improved cognitive impairment by blocking inflammation and apoptosis, improving synaptic factors, and diminishing tissue damage in the mPFC ischemic mice. |
| first_indexed | 2024-03-08T17:22:36Z |
| format | Article |
| id | doaj.art-4c4f176d2fa74797bf66eed4f75d3b36 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-08T17:22:36Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-4c4f176d2fa74797bf66eed4f75d3b362024-01-03T04:11:07ZengElsevierBrain Research Bulletin1873-27472022-04-011813645Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factorsFatemehsadat Seyedaghamiri0Leila Hosseini1Sareh Kazmi2Javad Mahmoudi3Dariush Shanehbandi4Abbas Ebrahimi-Kalan5Reza Rahbarghazi6Saeed Sadigh-Eteghad7Mehdi Farhoudi8Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Neuroscience, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IranNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Neuroscience, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Neuroscience, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Correspondence to: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran.Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Correspondence to: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran.Ischemia in the medial prefrontal cortex (mPFC) causes cognitive impairment in stroke cases. This study aimed to examine the effects of varenicline as α7 and α4β2 nicotine acetylcholine receptors (nAChRs) agonist, on cognitive impairment, inflammation, apoptosis, and synaptic dysfunction in mPFC ischemia. Mice were divided to three groups of control, sham, or photothrombotic mPFC ischemia model. The control and sham groups received 2 ml/kg of normal saline for a 14-day period. As well, the animals in the ischemia groups received normal saline (2 ml/kg) or varenicline at 0.1, 1, and 3 mg/kg doses for a 14-day period. Anxiety-like behaviors were then assessed by open field (OFT) and elevated plus-maze (EPM) tests. Memory was also evaluated using Morris water maze (MWM) and novel object recognition (NOR) tests. The levels of inflammatory (IL-1β, TNF-α), apoptotic (Bax, caspase3, BCL-2), and synaptic (SYP, PSD-95, and GAP-43) proteins were examined using the western blot method. In addition, the histological evaluation was performed to assess tissue damage. The administration of Varenicline at the dose of 3 mg/kg reduced the IL-1β, TNF-α, Bax, and caspase3 levels. Moreover, it increased BCL-2, SYP, PSD-95, and GAP-43 levels at the same dose and ameliorated memory impairment and anxiety-like behaviors in mPFC ischemic mice. Varenicline improved cognitive impairment by blocking inflammation and apoptosis, improving synaptic factors, and diminishing tissue damage in the mPFC ischemic mice.http://www.sciencedirect.com/science/article/pii/S0361923022000144Brain ischemiaVareniclineMedial prefrontal cortexMemoryAnxiety |
| spellingShingle | Fatemehsadat Seyedaghamiri Leila Hosseini Sareh Kazmi Javad Mahmoudi Dariush Shanehbandi Abbas Ebrahimi-Kalan Reza Rahbarghazi Saeed Sadigh-Eteghad Mehdi Farhoudi Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors Brain Research Bulletin Brain ischemia Varenicline Medial prefrontal cortex Memory Anxiety |
| title | Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors |
| title_full | Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors |
| title_fullStr | Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors |
| title_full_unstemmed | Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors |
| title_short | Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors |
| title_sort | varenicline improves cognitive impairment in a mouse model of mpfc ischemia the possible roles of inflammation apoptosis and synaptic factors |
| topic | Brain ischemia Varenicline Medial prefrontal cortex Memory Anxiety |
| url | http://www.sciencedirect.com/science/article/pii/S0361923022000144 |
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