Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors

• Published in: Brain research bulletin Vol. 181; pp. 36 - 45
• Main Authors: Seyedaghamiri, Fatemehsadat, Hosseini, Leila, Kazmi, Sareh, Mahmoudi, Javad, Shanehbandi, Dariush, Ebrahimi-Kalan, Abbas, Rahbarghazi, Reza, Sadigh-Eteghad, Saeed, Farhoudi, Mehdi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022; Elsevier
• Subjects: Animals; Anxiety; Anxiety - drug therapy; Anxiety - etiology; Apoptosis - drug effects; Behavior, Animal - drug effects; Brain ischemia; Brain Ischemia - complications; Brain Ischemia - immunology; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - immunology; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - physiopathology; Disease Models, Animal; Medial prefrontal cortex; Memory; Mice; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - immunology; Neuroinflammatory Diseases - metabolism; Neuroinflammatory Diseases - physiopathology; Nicotinic Agonists - administration & dosage; Nicotinic Agonists - pharmacology; Prefrontal Cortex - drug effects; Prefrontal Cortex - immunology; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Synapses - drug effects; Synapses - metabolism; Varenicline; Varenicline - administration & dosage; Varenicline - pharmacology; Brain ischemia; Medial prefrontal cortex; Anxiety; Varenicline; Memory
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2022.01.010

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. •Varenicline improves learning and memory impairment in the mouse model of mPFC ischemia.•Varenicline blocks inflammation and apoptosis in the mouse model of mPFC ischemia.•Varenicline improves synaptic dynamics in the mouse model of mPFC ischemia.•Varenicline diminishes tissue damage in the mouse model of mPFC ischemia.