title: Lovastatin fails to improve motor performance and survival inmethyl-CpG-binding protein2-null mice.
abstract: Previous studies provided evidence for the alteration of brain cholesterol homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The efficacy of statins in improving motor symptoms and prolonging survival of mutant mice suggested a potential role of statins in the therapy of Rett syndrome. In the present study, we show thatMecp2deletion had no effect on brain and reduced serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the previous study) had no effects on motor deficits and survival whenMecp2deletion was expressed on a background strain (C57BL/6J; B6) differing from that used in the earlier study. These findings indicate that the effects of statins may be background specific and raise important issues to consider when contemplating clinical trials. The reduction of the brain cholesterol metabolite 24S-hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence of changes in brain cholesterol metabolism and the potential utility of using plasma levels of 24S-OHC as a biomarker of brain cholesterol homeostasis in RTT.
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Claudia
authors.identifier: http://orcid.org/0000-0001-6334-9013
authors.initials: C
authors.lastname: Villani
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sacchetti
authors.affiliation: Analytical Instrumentation Unit, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Bagnati
authors.affiliation: Analytical Instrumentation Unit, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Passoni
authors.affiliation: Genetics of Neurodegenerative Diseases Unit, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fusco
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Carli
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Roberto William
authors.identifier: http://orcid.org/0000-0002-6017-9781
authors.initials: RW
authors.lastname: Invernizzi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008148:Lovastatin / Q000008:administration & dosage*; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009038:Motion; D015518:Rett Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D008148:Lovastatin
keywords: 24S-hydroxycholesterol; Mecp2; Rett syndrome; cholesterol metabolism; genetic background; lovastatin; mouse; neuroscience