Contribution of cholinergic system and Nrf2/HO-1 signaling to the anti-amnesic action of 7-fluoro-1,3-diphenylisoquinoline-1-amine in mice

https://doi.org/10.1016/j.cbi.2020.108959Get rights and content
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Highlights

  • FDPI treatment was effective against memory impairment induced by scopolamine in mice.

  • FDPI modulated AChE and M1 receptor contents in mice exposed to scopolamine.

  • FDPI reversed oxidative stress induced by scopolamine in prefrontal cortex of mice.

  • Oxidative stress and Nrf2/HO-1 signaling contributed to the action of FDPI.

Abstract

The isoquinoline 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) has been studied due to its multitarget properties, such as modulation of GABAergic and glutamatergic systems, antioxidant, and anti-inflammatory. This study investigated the contribution of oxidative stress, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase (HO-1) signaling, and the cholinergic system to the anti-amnesic action of FDPI in mice. Adult male Swiss mice received FDPI for 5 days (5–25 mg/kg, i.g.); the animals received scopolamine (1 mg/kg, i.p) from day 3–5. The vehicle-control group was carried out. Afterward, mice performed object recognition tests (ORTs). Scopolamine induced amnesia and cholinergic dysfunction by increasing the acetylcholinesterase (AChE) activity and content, decreasing the muscarinic M1 receptor levels in the prefrontal cortex and hippocampus of mice. This study reveals that scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice. Whereas the prefrontal cortex was susceptible to oxidative stress, none of the parameters evaluated was altered in the hippocampus of scopolamine-treated mice. FDPI at doses of 10 and 25 mg/kg had an anti-amnesic effect in the ORT tests. FDPI 10 mg/kg reversed the increase in the AChE activity and content, oxidative stress parameters, and modulated Nrf2/HO-1 signaling in the prefrontal cortex of scopolamine-exposed mice. Pearson's correlation analyses reinforced the contribution of the prefrontal cortical cholinergic system, oxidative stress as well as Nrf2/HO-1 signaling in the anti-amnesic effect of FDPI. Considering FDPI effects on the hippocampus, it was effective against the cholinergic dysfunction, AChE activity and content, and M1 receptor levels, which collectively could contribute to its anti-amnesic effect.

Keywords

Amnesia
Scopolamine
Isoquinoline
Nrf2/HO-1
Cholinergic
Oxidative stress

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