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 Ca²⁺ 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.

Keywords::

• Alzheimer's disease
• apoptosis
• Aβ
• neuroprotective effect
• oxidative stress
• β-hydroxybutyrate

Acknowledgements

The expenses of this work were supported by the Natural Science Foundation of China (31101865).

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.