title: Combination effects of sodium butyrate and pyridoxine treatment on cell proliferation and neuroblast differentiation in the dentate gyrus of D-galactose-induced aging model mice.
abstract: We previously reported that sodium butyrate (SB), a histone deacetylase inhibitor, robustly increased pyridoxine-induced cell proliferation and neuroblast differentiation in the dentate gyrus of the adult mouse. In this study, we investigated the effects of treatment with SB combined with pyridoxine on cell proliferation and neuroblast differentiation in the dentate gyrus of a mouse model of aging induced by D: -galactose (D: -gal). D: -gal was administered to 20-week-old male mice (D: -gal mice) for 10 weeks to induce changes that resemble natural aging in animals. Seven weeks after D: -gal (100 mg/kg) treatment, vehicle (physiological saline; D: -gal-vehicle mice) and SB (300 mg/kg) combined with pyridoxine (Pyr; 350 mg/kg) were administered to the mice (D: -gal-Pyr-SB mice) for 3 weeks. Escape latency under water maze in the D: -gal mice was longer than that in the control mice. In the D: -gal-Pyr-SB mice, escape latency was similar to that in the control mice. In the D: -gal mice, many cells in the granule cell layer of the dentate gyrus showed pyknosis and condensation of the cytoplasm. However, in the D: -gal-Pyr-SB mice, such cellular changes were rarely found. Furthermore, the D: -gal mice showed a great reduction in cell proliferation (Ki67-positive cells) and neuroblast differentiation (doublecortin-positive neuroblasts) in the dentate gyrus compared to control mice. However, in the D: -gal-Pyr-SB mice, cell proliferation and neuroblast differentiation were markedly increased in the dentate gyrus. Furthermore, the administration of pyridoxine with sodium butyrate significantly increased Ser133-phosphorylated cyclic AMP response element binding protein in the dentate gyrus. These results indicate that the combination treatment of Pyr with SB in D: -gal mice ameliorated the D: -gal-induced reduction in cell proliferation, neuroblast differentiation, and memory deficits.
authors: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors: Dae Young
authors: DY
authors: Yoo
authors: Woosuk
authors: W
authors: Kim
authors: In Hye
authors: IH
authors: Kim
authors: Sung Min
authors: SM
authors: Nam
authors: Jin Young
authors: JY
authors: Chung
authors: Jung Hoon
authors: JH
authors: Choi
authors: Yeo Sung
authors: YS
authors: Yoon
authors: Moo-Ho
authors: MH
authors: Won
authors: In Koo
authors: IK
authors: Hwang
mesh_terms: D000375:Aging; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects*; D005690:Galactose / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects*; D011736:Pyridoxine / Q000494:pharmacology*
chemical_list: D002087:Butyrates; D011736:Pyridoxine; D005690:Galactose