Skip to main content
Log in

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

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Srivastava N, Seth K, Srivastava N, Khanna VK, Agrawal AK (2008) Functional restoration using basic fibroblast growth factor (bFGF) infusion in Kainic acid induced cognitive dysfunction in rat: neurobehavioural and neurochemical studies. Neurochem Res 33:1169–1177

    Article  PubMed  CAS  Google Scholar 

  2. Goodman T, Trouche S, Massou I et al (2010) Young hippocampal neurons are critical for recent and remote spatial memory in adult mice. Neuroscience 171:769–778

    Article  PubMed  CAS  Google Scholar 

  3. Koehl M, Abrous DN (2011) A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci 33:1101–1114

    Article  PubMed  Google Scholar 

  4. Heine VM, Maslam S, Joëls M, Lucassen PJ (2004) Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging 25:361–375

    Article  PubMed  CAS  Google Scholar 

  5. Hwang IK, Yoo KY, Li H et al (2007) Differences in doublecortin immunoreactivity and protein levels in the hippocampal dentate gyrus between adult and aged dogs. Neurochem Res 32:1604–1609

    Article  PubMed  CAS  Google Scholar 

  6. Hwang IK, Yoo KY, Yi SS et al (2008) Age-related differentiation in newly generated DCX immunoreactive neurons in the subgranular zone of the gerbil dentate gyrus. Neurochem Res 33:867–872

    Article  PubMed  CAS  Google Scholar 

  7. Kuhn HG, Dickinson-Anson H, Gage F (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033

    PubMed  CAS  Google Scholar 

  8. Rao MS, Hattiangady B, Shetty AK (2006) The window and mechanisms of major age-related decline in the production of new neurons within the dentate gyrus of the hippocampus. Aging Cell 5:545–558

    Article  PubMed  CAS  Google Scholar 

  9. Seki T, Arai Y (1995) Age-related production of new granule cells in the adult dentate gyrus. Neuroreport 6:2479–2482

    Article  PubMed  CAS  Google Scholar 

  10. Chiu CS, Deng JS, Hsieh MT et al (2009) Yam (Dioscorea pseudojaponica Yamamoto) ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by d-galactose. Am J Chin Med 37:889–902

    Article  PubMed  CAS  Google Scholar 

  11. Luo Y, Niu F, Sun Z et al (2009) Altered expression of Aβ metabolism-associated molecules from d-galactose/AlCl3 induced mouse brain. Mech Ageing Dev 130:248–252

    Article  PubMed  CAS  Google Scholar 

  12. Tian J, Ishibashi K, Ishibashi K et al (2005) Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: a comprehensive transcriptional response. Proc Natl Acad Sci USA 102:11846–11851

    Article  PubMed  CAS  Google Scholar 

  13. Zhong SZ, Ge QH, Qu R, Li Q, Ma SP (2009) Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice. J Neurol Sci 277:58–64

    Article  PubMed  CAS  Google Scholar 

  14. Shen YX, Xu SY, Wei W et al (2002) Melatonin reduces memory changes and neural oxidative damage in mice treated with d-galactose. J Pineal Res 32:173–178

    Article  PubMed  CAS  Google Scholar 

  15. Wei H, Li L, Song Q, Ai H, Chu J, Li W (2005) Behavioural study of the d-galactose induced aging model in C57BL/6 J mice. Behav Brain Res 157:245–251

    Article  PubMed  CAS  Google Scholar 

  16. Xu XH, Zhao TQ (2002) Effects of puerarin on d-galactose-induced memory deficits in mice. Acta Pharmacol Sin 23:587–590

    PubMed  CAS  Google Scholar 

  17. Cui X, Zuo P, Zhang Q et al (2006) Chronic systemic d-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-α-lipoic acid. J Neurosci Res 84:647–654

    Article  PubMed  CAS  Google Scholar 

  18. Hsieh HM, Wu WM, Hu ML (2009) Soy isoflavones attenuate oxidative stress and improve parameters related to aging and Alzheimer’s disease in C57BL/6 J mice treated with d-galactose. Food Chem Toxicol 47:625–632

    Article  PubMed  CAS  Google Scholar 

  19. Zhang Q, Huang Y, Li X, Cui X, Zuo P, Li J (2005) GM1 ganglioside prevented the decline of hippocampal neurogenesis associated with d-galactose. Neuroreport 16:1297–1301

    Article  PubMed  CAS  Google Scholar 

  20. Zhang Q, Li X, Cui X, Zuo P (2005) d-Galactose injured neurogenesis in the hippocampus of adult mice. Neurol Res 27:552–556

    Article  PubMed  CAS  Google Scholar 

  21. Song X, Bao M, Li D, Li YM (1999) Advanced glycation in d-galactose induced mouse aging model. Mech. Ageing Dev 108:239–251

    Article  CAS  Google Scholar 

  22. Alarcón JM, Malleret G, Touzani K et al (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42:947–959

    Article  PubMed  Google Scholar 

  23. Lattal KM, Barrett RM, Wood MA (2007) Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci 121:1125–1131

    Article  PubMed  CAS  Google Scholar 

  24. Levenson JM, O’Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279:40545–40559

    Article  PubMed  CAS  Google Scholar 

  25. Dokmanovic M, Marks PA (2005) Prospects: histone deacetylase inhibitors. J Cell Biochem 96:293–304

    Article  PubMed  CAS  Google Scholar 

  26. Yoo DY, Kim W, Kim DW et al (2011) Pyridoxine enhances cell proliferation and neuroblast differentiation by upregulating the GABAergic system in the mouse dentate gyrus. Neurochem Res 36:713–721

    Article  PubMed  CAS  Google Scholar 

  27. Yoo DY, Kim W, Nam SM et al (2011) 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. Neurochem Res 36:1850–1857

    Article  PubMed  CAS  Google Scholar 

  28. Brown JP, Couillard-Després S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10

    Article  PubMed  CAS  Google Scholar 

  29. Couillard-Despres S, Winner B, Schaubeck S et al (2005) Doulecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci 21:1–14

    Article  PubMed  Google Scholar 

  30. Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  31. Wei H, Cai Y, Chu J, Li C, Li L (2008) Temporal gene expression profile in hippocampus of mice treated with d-galactose. Cell Mol Neurobiol 28:781–794

    Article  PubMed  CAS  Google Scholar 

  32. Kumar A, Prakash A, Dogra S (2010) Naringin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by d-galactose in mice. Food Chem Toxicol 48:626–632

    Article  PubMed  CAS  Google Scholar 

  33. Kilgore M, Miller CA, Fass DM et al (2010) Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 35:870–880

    Article  PubMed  CAS  Google Scholar 

  34. Riggs KM, Spiro A 3rd, Tucker K, Rush D (1996) Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 63:306–314

    PubMed  CAS  Google Scholar 

  35. Eriksson PS, Perfilieva E, Björk-Eriksson T et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317

    Article  PubMed  CAS  Google Scholar 

  36. Dakshinamurti K, Paulose CS, Viswanathan M, Siow YL, Sharma SK, Bolster B (1990) Neurobiology of pyridoxine. Ann N Y Acad Sci 585:128–144

    Article  PubMed  CAS  Google Scholar 

  37. Kirksey A, Morré DM, Wasynczuk AZ (1990) Neuronal development in vitamin B6 deficiency. Ann N Y Acad Sci 585:202–218

    Article  PubMed  CAS  Google Scholar 

  38. Guan JS, Haggarty SJ, Giacometti E et al (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60

    Article  PubMed  CAS  Google Scholar 

  39. Vecsey CG, Hawk JD, Lattal KM et al (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci 27:6128–6140

    Article  PubMed  CAS  Google Scholar 

  40. Wood MA, Attner MA, Oliveira AM, Brindle PK, Abel T (2006) A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes. Learn Mem 13:609–617

    Article  PubMed  CAS  Google Scholar 

  41. Izquierdo LA, Barros DM, Vianna MR et al (2002) Molecular pharmacological dissection of short-and long-term memory. Cell Mol Neurobiol 22:269–287

    Article  PubMed  CAS  Google Scholar 

  42. Silva AJ, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21:127–148

    Article  PubMed  CAS  Google Scholar 

  43. Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79:59–68

    Article  PubMed  CAS  Google Scholar 

  44. Impey S, Mark M, Villacres EC, Poser S, Chavkin C, Storm DR (1996) Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus. Neuron 16:973–982

    Article  PubMed  CAS  Google Scholar 

  45. Mizuno M, Yamada K, Maekawa N, Saito K, Seishima M, Nabeshima T (2002) CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning. Behav Brain Res 133:135–141

    Article  PubMed  CAS  Google Scholar 

  46. Schulz S, Siemer H, Krug M, Höllt V (1999) Direct evidence for biphasic cAMP responsive element-binding protein phosphorylation during long-term potentiation in the rat dentate gyrus in vivo. J Neurosci 19:5683–5692

    PubMed  CAS  Google Scholar 

  47. Florian C, Mons N, Roullet P (2006) CREB antisense oligodeoxynucleotide administration into the dorsal hippocampal CA3 region impairs long- but not short-term spatial memory in mice. Learn Mem 13:465–472

    Article  PubMed  CAS  Google Scholar 

  48. Guzowski JF, McGaugh JL (1997) Antisense oligodeoxynucleotide-mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training. Proc Natl Acad Sci USA 94:2693–2698

    Article  PubMed  CAS  Google Scholar 

  49. Huang YY, Pittenger C, Kandel ER (2004) A form of long-lasting, learning-related synaptic plasticity in the hippocampus induced by heterosynaptic low-frequency pairing. Proc Natl Acad Sci USA 101:859–864

    Article  PubMed  CAS  Google Scholar 

  50. Pittenger C, Huang YY, Paletzki RF et al (2002) Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory. Neuron 34:447–462

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mr. Seung Uk Lee and Mrs. Hyun Sook Kim for their technical help in this study. This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST), Republic of Korea (2010-0007711).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Moo-Ho Won or In Koo Hwang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoo, D.Y., Kim, W., Kim, I.H. et al. 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. Neurochem Res 37, 223–231 (2012). https://doi.org/10.1007/s11064-011-0597-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0597-9

Keywords

Navigation