title: Ferulic Acid Improves Cognitive Skills Through the Activation of the Heme Oxygenase System in the Rat.
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.
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mhillaj
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Catino
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Fiorella M
authors.initials: FM
authors.lastname: Miceli
authors.affiliation: Institute of Microbiology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Santangelo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Trabace
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy. cesare.mancuso@unicatt.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Mancuso
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects*
chemical_list: D003373:Coumaric Acids; D008665:Metalloporphyrins; D011524:Protoporphyrins; D003346:Corticotropin-Releasing Hormone; C004999:ferulic acid; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase
keywords: Biliverdin reductase; Emotional arousal; Ferulic acid; Heme oxygenase; Rat brain