Pyridoxine Enhances Cell Proliferation and Neuroblast Differentiation by Upregulating the GABAergic System in the Mouse Dentate Gyrus

Abstract

We investigated the effects of pyridoxine (vitamin B(6)) on cell death, cell proliferation, neuroblast differentiation, and the GABAergic system in the mouse dentate gyrus. We administered pyridoxine (350 mg/kg intraperitoneally) to 8 week old mice twice a day for 14 days and sacrificed them at 10 weeks of age. Pyridoxine treatment did not induce neuronal death or activate microglia in the dentate gyrus, while glial fibrillary acidic protein (GFAP)-positive cells were significantly increased in the subgranular zone of the dentate gyrus. The increase in GFAP-positive cells was confirmed to be due to proliferating cells based on double immunofluorescence staining. GFAP-positive cells, which were also labeled with Ki67, a marker for cell proliferation, and doublecortin, a marker for neuroblast differentiation, were significantly increased in the pyridoxine-treated group compared to those in the vehicle-treated group. Pyridoxine treatment also increased the protein levels of glutamic acid decarboxylase (GAD) 67, an enzyme for GABA synthesis, and pyridoxal 5'-phosphate (PNP) oxidase, an enzyme for pyridoxal phosphate synthesis, in the dentate gyrus. These results suggest that pyridoxine treatment distinctly increases cell proliferation, neuroblast differentiation, and upregulated the GABAergic system, as revealed by the increases of GAD67 and PNP oxidase in the mouse dentate gyrus.

Synergistic Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on Increase of Neurogenesis Induced by Pyridoxine and Increase of Neural Proliferation in the Mouse Dentate Gyrus

“…However, a few studies have been conducted on these effects in combination with other factors. In a previous study, we observed that pyridoxine (Pyr, vitamin B 6 ) significantly increased cell proliferation and neuroblast differentiation in the mouse dentate gyrus without any neuronal damage [26]. In the present study, therefore, we observed effects of sodium butyrate (SB), a HDAC inhibitor, on neurogenesis induced by Pyr and increase of neural proliferation in the mouse dentate gyrus.…”

Reversible aberration of neurogenesis targeting late-stage progenitor cells in the hippocampal dentate gyrus of rat offspring after maternal exposure to acrylamide

“…In our laboratory, increase in reelinproducing interneurons in the hilus has recently been shown in a rat model of neuronal mismigration induced by developmental hypothyroidism (Saegusa et al 2010). Recently, increasing numbers of chemicals have revealed to affect proliferation and differentiation of progenitor cells by exposure to mice or rats during postnatal life Hwang et al 2011;Nam et al 2011;Yan et al 2011;Yoo et al 2011). Because neurogenesis in the dentate gyrus is rather active during the developmental stage than the adult stage, developmental exposure to such chemicals may risk stronger impact on neurogenesis.…”

Effects of S-Allyl-L-Cysteine on Cell Proliferation and Neuroblast Differentiation in the Mouse Dentate Gyrus

“…For immunohistochemistry, vehicle (n=7)-and SAC (n=7)-treated animals were anesthetized with mixture of tiletamine hypochloride and zolazepam hydroxide (30 mg/ kg, Virbac, Carros, France) and immunohistochemistry for Ki67 and DCX was processed under the same conditions according to a previous study [40]. Briefly, the tissue sections were selected apart from each other in 90 μm between -1.46 mm and -2.46 mm posterior to the bregma in reference to the mouse atlas [9] for each animal.…”

“…The dendritic complexity of the DCX-positive cells was traced using camera lucida at 100 × magnification (Neurolucida; MicroBrightField, Williston, VT, U.S.A.). DCX-positive cells were separated into 2 categories according to dendritic complexity [40]. The cell counts from all of the sections of all of the mice were averaged.…”

“…For western blot analysis for 5-HT 1A receptor 5 animals in each group were used according to a previous study [40]. Briefly, After electrophoresis, the gels were transferred to nitrocellulose transfer membranes (Pall Crop, East Hills, NY, U.S.A.) and membrane was incubated with mouse anti-5-HT 1A receptor (1:400; Chemicon International, Temecula, CA, U.S.A.), peroxidase-conjugated anti-mouse IgG (Sigma) and an enhanced luminol-based chemiluminescent (ECL) kit (Pierce Chemical, Rockford, IL, U.S.A.).…”