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Ferulic Acid Improves Cognitive Skills Through the Activation of the Heme Oxygenase System in the Rat

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Abstract

Over the last years, many studies reported on the antioxidant effects of ferulic acid (FA) in preclinical models of dementia through the activation of the heme oxygenase/biliverdin reductase (HO/BVR) system. However, only a few studies evaluated whether FA could improve neurological function under milder conditions, such as psychological stress. The aim of this study was to investigate the effects of FA (150 mg/kg intraperitoneal route) on cognitive function in male Wistar rats exposed to emotional arousal. Animals were randomly assigned to two experimental groups, namely not habituated or habituated to the experimental context, and the novel object recognition test was used to evaluate their cognitive performance. The administration of FA significantly increased long-term retention memory in not habituated rats. Ferulic acid increased the expression of HO-1 in the hippocampus and frontal cortex of not habituated rats only, whereas HO-2 resulted differently modulated in these cognitive brain areas. No significant effects on either HO-1 or HO-2 or BVR were observed in the cerebellum of both habituated and not habituated rats. Ferulic acid activated the stress axis in not habituated rats, as shown by the increase in hypothalamic corticotrophin-releasing hormone levels. Pre-treatment with Sn-protoporphyrin-IX [0.25 μmol/kg, intracerebroventricular route (i.c.v.)], a well-known inhibitor of HO activity through which carbon monoxide (CO) and biliverdin (BV) are generated, abolished the FA-induced improvement of cognitive performance only in not habituated rats, suggesting a role for HO-derived by-products. The CO-donor tricarbonyldichlororuthenium (II) (30 nmol/kg i.c.v.) mimicked the FA-related improvement of cognitive skills only in not habituated rats, whereas BV did not have any effect in any group. In conclusion, these results set the stage for subsequent studies on the neuropharmacological action of FA under conditions of psychological stress.

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Acknowledgments

This work was supported by Fondi Ateneo from Catholic University to C.M.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

    Emanuela Mhillaj & Vincenzo Cuomo

  2. Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy

    Stefania Catino, Fiorella M. Miceli & Cesare Mancuso

  3. Institute of Microbiology, Catholic University School of Medicine, Rome, Italy

    Rosaria Santangelo

  4. Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

    Luigia Trabace

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  1. Emanuela Mhillaj
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  2. Stefania Catino
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Correspondence to Cesare Mancuso.

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Vincenzo Cuomo and Cesare Mancuso share senior authorship

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Mhillaj, E., Catino, S., Miceli, F.M. et al. Ferulic Acid Improves Cognitive Skills Through the Activation of the Heme Oxygenase System in the Rat. Mol Neurobiol 55, 905–916 (2018). https://doi.org/10.1007/s12035-017-0381-1

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