title: Effects of lifestyle modifications on cognitive impairments in a mouse model of hypercholesterolemia.
abstract: Epidemiological studies indicate that high midlife plasma cholesterol levels increases the risk of Alzheimer's disease. Moreover, middle-aged familial hypercholesterolemia (FH) subjects show a particularly high incidence of mild cognitive impairments (MCI). These evidence points to hypercholesterolemia as one of the modifiable risk factors focused on prevention/treatment of cognitive deterioration. The present study draws a comparison between pharmacological (lipid-lowering drug probucol) and non-pharmacological (voluntary running wheel, RW) approaches for the management of hypercholesterolemia and cognitive impairments associated with the low-density lipoprotein receptor-deficient (LDLr(-/-)) mice, a well-established rodent model of FH. We also investigated whether exposure to environmental enrichment (EE), a feasible option to increase physical activity in young mice cohort, from birth to adolescence (PN45) yields long-term behavioral changes in adult LDLr(-/-) mice (PN90). We observed that both probucol and RW significantly decreased total and non-HDL plasma cholesterol levels in LDLr(-/-) mice. Notably, only physical exercise mitigated the spatial memory deficits of LDLr(-/-) mice. In addition, we showed that exposure to EE from birth until the adolescence did not mitigate the spatial memory deficits of adult LDLr(-/-) mice in the object location task, although it induced persistent anxyolitic-like effects in the open field arena. Collectively, our results emphasize the advantages physical exercise, in comparison to lipid-lowering drugs, for the management of cognitive deficits associated with FH.
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil. eduardoluiz26@gmail.com
authors.forename: Eduardo Luiz Gasnhar
authors.initials: EL
authors.lastname: Moreira
authors.forename: Aderbal S
authors.initials: AS
authors.lastname: Aguiar
authors.forename: Cristiane Ribeiro
authors.initials: CR
authors.lastname: de Carvalho
authors.forename: Danúbia Bonfanti
authors.initials: DB
authors.lastname: Santos
authors.forename: Jade
authors.initials: J
authors.lastname: de Oliveira
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Xikota
authors.forename: Roger
authors.initials: R
authors.lastname: Walz
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology* / Q000628:therapy; D018703:Founder Effect; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy / Q000523:psychology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D010805:Physical Conditioning, Animal; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use; D011973:Receptors, LDL / Q000235:genetics; D012931:Social Environment
chemical_list: D000924:Anticholesteremic Agents; D011973:Receptors, LDL; D011341:Probucol