The effect of varenicline on cognitive impairment, inflammation, apoptosis, neurotrophic factors and synaptic dynamics in the photothrombotic model of mPFC ischemia in BALB/c mice

Abstract

Introduction: This study aims to investigate the dose-dependent effect of varenicline as an agonist of nicotinic acetylcholine receptors and a protective agent of the nervous system on cognitive impairments, inflammation, apoptosis and synaptic dynamics in the photothrombosis ischemia model in the middle prefrontal cortex of male BALB/c mice was done. Materials and methods: 72 adult male BALB/c mice were divided into control, sham and photothrombotic ischemia groups in the mPFC region. The control and sham groups received normal saline for 14 days. Also, the ischemic groups received normal saline at dose of 2 mg/kg or varenicline with doses of 3 and 1, 0.1 mg/kg for 14 days. All groups received normal saline or varenicline orally by gavage. Anxiety-like behaviors of animals were investigated through the open field and elevated plus maze tests. Morris water maze and novel object recognition tests were used to investigate spatial and episodic memory in animals. The levels of inflammatory factors (IL-1β, TNF-α), apoptotic factors (Bax, caspase3, BCL-2) and synaptic proteins (SYP, PSD-95, GAP-43) were measured by western blot method. BDNF neurotrophic factor levels were evaluated by ELISA method. H&E staining method was also used to evaluate tissue damage. Result: According to our results, varenicline (3 mg/kg) decreased the levels of IL-1β, TNF-α, Bax and caspase 3 in mice with ischemia in the mPFC region. Also, it increased the levels of BCL-2, BDNF, SYP, PSD-95 and GAP-43 and improved memory impairment and anxiety-like behaviors. Conclusion: The findings of this research showed that varenicline (3 mg/kg) probably has a protective role against cognitive impairm ents caused by mPFC ischemia through the reduction of inflammatory and apoptotic factors, as well as the improvement of synaptic dynamics and the increase of the neurotrophic factor.