title: The neuroprotective effects of β-hydroxybutyrate on Aβ-injected rat hippocampus in vivo and in Aβ-treated PC-12 cells in vitro.
abstract: Alzheimer's disease is a neurodegenerative disorder associated with the deposition of the peptide amyloid-beta (Aβ) in senile plaques and cerebral vasculature. The neurotoxic mechanisms of this condition have been linked to oxidative-stress-induced apoptosis leading to widespread neuronal loss. Herein, we demonstrate the neuroprotective effects of a ketone body D-β-hydroxybutyrate (β-HB) in neural cell lines and an animal model induced by injecting Aβ into the hippocampus. Using histological examination and the TUNEL assay, we show that administration of exogenous β-HB effectively prevents Aβ deposition and neuron apoptosis in this rat model. β-HB pretreatment also relieves the oxidative stress in Aβ-induced PC-12 cells, as shown by decreased intracellular reactive oxygen species and Ca(2+) levels, activated Nrf2 and recovered superoxide dismutase and catalase activities. Consequently, the apoptotic pathway is also inhibited in these cells, with decreased levels of p53, caspase-12, caspase-9, caspase-3; a decreased Bax/Bcl-2 ratio; and decreased cytochrome c release. Taken together, our study provides a molecular basis for the neuroprotective effects of β-HB in line with the suppression of oxidative stress and the inhibition of apoptotic protein activation.
authors.affiliation: College of Veterinary Medicine, Jilin University , Changchun, Jilin , P. R. China.
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.forename: W
authors.initials: W
authors.lastname: Tian
authors.forename: T
authors.initials: T
authors.lastname: Wei
authors.forename: F
authors.initials: F
authors.lastname: Liu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007267:Injections; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D020155:3-Hydroxybutyric Acid
keywords: Alzheimer's disease; Aβ; apoptosis; neuroprotective effect; oxidative stress; β-hydroxybutyrate