Effect of Bushen Huoxue acupuncture on cognitive function and silent information regulator 2 in hip-pocampal neurons of SAMP8 mice
Objective To investigate the effects of Bushen Huoxue acupuncture on cognitive function and the silent information regulator 2(SIRT2)-mediated reticulon 4B(RTN4B)/beta-site amyloid precursor protein cleaving enzyme 1(BACE1)pathway in hippocampal neurons of senescence-accelerated mouse prone 8(SAMP8)mice.Methods Six SAMR1 mice served as a normal control group,while 18 SAMP8 mice were randomly divided into three groups:a model control group,an acupuncture treatment group,and a non-acupuncture treatment group,with six mice in each group.The acupuncture treatment group received twisting and purging technique at Xuehai and Geshu,and twisting and tonifying technique at Shenshu and Baihui,with needle manipulation for 1 minute and re-tention for 10 minutes.The non-acupuncture treatment group underwent grasping stimulation at non-meridian and non-acupoint sites.All interventions lasted for 8 weeks.Cognitive function was evaluated using the Morris water maze test.Immunohistochemistry and enzyme-linked immunosorbent assay were used to assess the activation of hip-pocampal neuron and beta-amyloid protein(Aβ)deposition.Western blotting was used to examine the expression levels of SIRT2 pathway-related proteins,including SIRT2,RTN4B,BACE1,and beta-amyloid precursor protein C-terminal fragment(APP-CTF).Results Compared with the normal control group,the model control group showed prolonged escape latency,reduced time spent in the target quadrant,and decreased platform crossing times(P<0.05).Additionally,the model control group exhibited increased Aβ42 and CD68-positive areas in hippocampal tissue(P<0.01),elevated serum Aβ42 levels,significantly upregulated expression of SIRT2,BACE1,and APP-CTF,and downregulated expression of RTN4B(P<0.05).Compared with the model control group and the non-acupuncture treatment group,the acupuncture treatment group showed shortened escape latency on day 1 to day 5[day 1:(37.80±10.42)s vs.(49.80±6.14)s,(44.60±7.40)s,P<0.05;day 2:(36.80±12.69)s vs.(48.80±5.97)s,(44.20±7.72)s,P<0.05;day 3:(38.60±9.71)s vs.(51.20±5.54)s,(43.60±6.46)s,P<0.05;day 4:(36.00±11.20)s vs.(46.40±5.81)s,(45.20±7.36)s,P<0.05;day 5:(36.60±11.37)s vs.(47.80±5.31)s,(43.80±9.44)s,P<0.05],in-creased time spent in the target quadrant[(7.83±0.98)s vs.(1.00±0.63)s,(3.33±0.52)s,P<0.05],and increased platform crossings times[(13.33±1.03)vs.(3.17±1.17),(7.33±0.52),P<0.05].The acupuncture treatment group also showed decreased hippocampal Aβ42 and CD68-positive areas(P<0.01),decreased serum Aβ42 levels[(11.38±1.57)μg/mL vs.(23.14±2.41)μg/mL,(17.16±1.27)μg/mL,P<0.05],downregulated expression of SIRT2[(1.98±0.19)vs.(4.21±0.31),(3.22±0.23),P<0.05 or P<0.01],BACE1[(1.81±0.14)vs.(2.80±0.19),(2.43±0.13),P<0.05 or P<0.01],and APP-CTF[(2.56±0.26)vs.(4.53±0.33),(3.48±0.25),P<0.05 or P<0.01],as well as upregulated expres-sion of RTN4B[(0.79±0.06)vs.(0.27±0.03),(0.46±0.05),P<0.05 or P<0.01].Conclusion Bushen Huoxue acupuncture improves cognitive function and reduces Aβ deposition in SAMP8 mice by inhibiting the SIRT2-medi-ated RTN4B/BACE1 pathway.
MouseBushen Huoxue acupunctureAβ DepositionCognitive functionSilent information regula-tor 2Reticulon 4B/beta-site amyloid precursor protein cleaving enzyme 1