title: Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus.
abstract: Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate(C18),a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation.
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Lucas
authors.initials: L
authors.lastname: Canto de Souza
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Provensi
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Sesto Fiorentino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Sesto Fiorentino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Costa
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Scheila Daiane
authors.initials: SD
authors.lastname: Schmidt
authors.affiliation: Dipartimento di Scienze della Salute, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Passani
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Firenze, Italy. Electronic address: patrizio.blandina@unifi.it.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Blandina
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010649:Phenylalanine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011726:Pyridinium Compounds / Q000494:pharmacology; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C504985:1-N-(4-sulfamoylphenylethyl)-2,4,6-trimethylpyridinium; D002257:Carbonic Anhydrase Inhibitors; D011726:Pyridinium Compounds; D013449:Sulfonamides; D010649:Phenylalanine; D048049:Extracellular Signal-Regulated MAP Kinases; D002256:Carbonic Anhydrases; D000086:Acetazolamide
keywords: 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-Trimethylpyridinium perchlorate; Acetazolamide; d-phenylalanine