title: The Effects of LW-AFC on the Hippocampal Transcriptome in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer's Disease.
abstract: The senescence-accelerated mouse prone 8 (SAMP8) strain is considered a robust experimental model for developing preventative and therapeutic treatments for Alzheimer's disease (AD), a neurodegenerative disease which cannot be effectively prevented, halted, or cured. Our previous studies showed that LW-AFC, a new formula derived from the classical traditional Chinese medicinal prescription Liuwei Dihuang decoction, ameliorates cognitive deterioration in PrP-hAβPPswe/PS1ΔE9 transgenic mice and SAMP8 mice. This study aims to investigate the mechanism that mediates how LW-AFC improves cognitive deficit on the basis of the transcriptome. We conducted a genome-wide survey of gene expression in the hippocampus in mice from the senescence accelerated mouse resistant 1 (SAMR1) strain, from SAMP8 and from LW-AFC treated SAMP8. The results showed that LW-AFC reversed the transcriptome in the hippocampus of SAMP8 mice. The specific investigation of altered gene expression in subtypes defined by cognitive profiles indicated that the systemic lupus erythematosus pathway, spliceosomes, amyotrophic lateral sclerosis, and the insulin signaling were involved in the improvement of cognitive ability by LW-AFC. The expression of genes Enpp2, Etnk1, Epdr1, and Gm5900 in the hippocampus were correlated with that of LW-AFC's ameliorating cognitive impairment in SAMP8 mice. Because LW-AFC is composed of polysaccharides, glycosides, and oligosaccharides, we infer that LW-AFC has direct or indirect effects on altering gene expressions and regulating pathways in the hippocampus of SAMP8 mice. These data are helpful for the enhanced identification of LW-AFC as new therapeutic modalities to AD.
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Shanyi
authors.initials: S
authors.lastname: Qiao
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ni
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D011897:Random Allocation; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; C042579:Liuwei Dihuang Decoction; D018697:Nootropic Agents
keywords: Alzheimer’s disease; LW-AFC; senescence-accelerated mouse prone 8 strain; traditional Chinese medicine; transcriptome