Objective To investigate the effect and mechanisms of β hydroxybutyrate (βOHB) regulation on p75NTR expression in Alzheimer's disease (AD) model cells.Methods First,cultured SH-SY5Y cells were exposed to Aβ (final concentrations:10,20,40,80 μmol/L) with or without 5 mmol/L βOHB pretreatment,and sham-treated cells were used as the control.At 24 h after treatment,the viability of cells was determined by the MTT assay.Secondly,cultured cells were divided into four groups.Cells in the Aβ group were exposed to Aβ (final concentration:20 μ mol/L)with or without 5 mmol/L βOHB pretreatment.Cells in the βOHB group were treated only with 5 mmol/L βOHB,and sham treated cells were used as the control.At 6 h and 24 h after treatment,the expression of p75NTR,HDAC1/2 mRNA and its protein expression,and p65 protein expression were measured by qRT-PCR or Western blot.Finally,the expression of p75NTR mRNA and protein was analyzed in cultured cells after silencing HDAC1 / 2 with siRNA.Results The viability of cells with 40 μmol/L or 80 μmol/L treatment was lower than that in the control group (P＜0.01),and there was a significant increase (P＜0.01) in cell viability of the βOHB intervention group,compared with the Aβ group.At 6 h or 24 h after treatment,the expression of p75NTR mRNA,its protein expression,and p65 protein expression were clearly increased in the βOHB group (P＜0.05) and markedly decreased (P＜0.01) in the Aβ group,compared with the control.Additionally,the expression of HDAC1 / 2 mRNA and protein was higher (P＜0.01) in the Aβ group at 6h or 24h after treatment and lower(P＜0.05 or P＜0.01)in the βOHB group at 6 h after treatment than in the control group.Compared with the Aβ group,there were significant increases (P＜0.01) observed in p75NTR mRNA,its protein expression,and p65 protein expression,and a notable decrease (P＜0.05) in HDAC1 / 2 mRNA and protein expression in cells of the βOHB intervention group at 6 h and 24 h after treatment.The expression of p75NTR mRNA and protein increased in HDAC1 knock-down cells compared with the control (P＜0.05).However,no difference was found in p75NTR expression in HDAC2 knock-down cells (P＞0.05).Conclusions βOHB up-regulates p75NTR expression by inhibiting HDAC1 of βOHB.It also activates p65 and prevents the decrease of cell viability.