title: β-alanyl-L-histidine rescues cognitive deficits caused by feeding a high fat diet in a transgenic mouse model of Alzheimer's disease.
abstract: Our goal in this study was to determine whether or not feeding young (4 months old) Alzheimer's disease model transgenic mice with a high fat diet (HFD), consisting of 32% fat, is capable of causing cognitive decline and whether treatment with β-alanyl-L-histidine (carnosine) is capable of reducing these effects. Carnosine is an endogenous antioxidant and antiglycating agent that is abundantly present in the brain and muscle tissues of vertebrates. After 8 weeks of feeding with HFD, we observed a significant decline in the contextual memory in transgenic mice fed with HFD as compared to transgenic mice fed with a normal diet as well as to normal diet-wild type mice. Treatment with carnosine at a dose of 5 mg/day for 6 weeks was effective in preventing cognitive decline, as the transgenic group fed with HFD and treated with carnosine displayed a level of cognition comparable to controls. No differences in senile plaque load were observed between all groups. However, we observed an increase in the expression of RAGE in blood vessels as well as increased microglial activation in the hippocampus of animals fed with HFD, effects that were reversed when treated with carnosine. Given these results, there is a possibility that inflammation and cerebrovascular abnormalities might be the cause of cognitive decline in this model.
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
authors.forename: Bruno
authors.initials: B
authors.lastname: Herculano
authors.forename: Minami
authors.initials: M
authors.lastname: Tamura
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ohba
authors.forename: Mayu
authors.initials: M
authors.lastname: Shimatani
authors.forename: Natsumaro
authors.initials: N
authors.lastname: Kutsuna
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Hisatsune
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D000818:Animals; D002336:Carnosine / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D002336:Carnosine