Ginsenoside Reduces Cognitive Impairment During Chronic Cerebral Hypoperfusion Through Brain-Derived Neurotrophic Factor Regulated by Epigenetic Modulation.
Increased expression of brain-derived neurotrophic factor (BDNF) has been associated with memory-enhancing and neuroprotective properties of some drugs under chronic cerebral hypoperfusion (CCH) condition. Ginsenoside Rd (GSRd), one of the main active ingredients in Panax ginseng, is widely used for brain protection. However, it is poorly understood whether epigenetic mechanisms implied in the BDNF modulation after GSRd treatment for CCH remain elusive. Here, we investigated the neuroprotective effects of GSRd and the involved mechanisms. We demonstrated that GSRd administration ameliorated CCH-induced impairment of learning and memory behaviors, evidenced by decreased escape latency and increased number of crossing the platform in Morris water maze test. This improvement was associated with promoted neuron survival and increased BDNF expression in the hippocampus and prefrontal cortex of CCH mice. GSRd improved neuron survival and decreased neuron apoptosis and the level of caspase-3 under oxygen-glucose deprivation/reoxygenation (OGD/R) by upregulation of BDNF as well as in vitro. The levels of acetylated histone H3 (Ac-H3) and histone deacetylase (histone deacetylase 2 (HDAC2)) were altered under OGD/R in a time-dependent manner, and GSRd reestablished the balance between Ac-H3 and HDAC2 which resulted in upregulation of BDNF and increased neuron survival. MS-275, an inhibitor of class I HDACs, abolished the levels of Ac-H3 at the bdnf promoters and enhanced upregulation of BDNF after GSRd administration, suggesting a synergistic effect between GSRd and MS-275. All the data suggested that GSRd provided neuroprotection by epigenetic modulation which accounted for the regulation of BDNF in CCH mice.
['Wan|Qun|Q|', 'Ma|Xue|X|', 'Zhang|Zhi-Jun|ZJ|', 'Sun|Ting|T|', 'Xia|Feng|F|', 'Zhao|Gang|G|', 'Wu|Yu-Mei|YM|']
D000107:Acetylation D000818:Animals D002545:Brain Ischemia D019208:Brain-Derived Neurotrophic Factor D050882:CREB-Binding Protein D002470:Cell Survival D002478:Cells, Cultured D002908:Chronic Disease D060825:Cognitive Dysfunction D044127:Epigenesis, Genetic D036145:Ginsenosides D005947:Glucose D006624:Hippocampus D056464:Histone Deacetylase 2 D006657:Histones D008297:Male D008810:Mice, Inbred C57BL D009474:Neurons D000066829:Neuroprotection D010100:Oxygen D065853:Spatial Learning D050880:p300-CBP Transcription Factors
Chronic cerebral hypoperfusion Brain-derived neurotrophic factor Epigenetic Ginsenoside Rd Histone H3 HDAC2