Skip to main content

Advertisement

Log in

Co-location of HDAC2 and Insulin Signaling Components in the Adult Mouse Hippocampus

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

As one part of epigenetics, histone deacetylases (HDACs) have been demonstrated to get into the neural events, including neurogenesis, synaptic plasticity, and neurodegeneration through regulating acetylation status of target proteins to influence protein function and gene expression. However, the recent studies indicated that HDAC2, a member of HDACs family, played a role in insulin signaling pathway and synaptic plasticity. Here, we are concerned about whether HDAC2 was co-located with insulin signaling components in postsynaptic glutamatergic neurons (PSGNs) of the adult mouse hippocampus using double immunofluorescence staining. The results displayed that HDAC2 was present in PSGNs marked by N-methyl-d-aspartate receptor subunit 2B, in which major components of insulin signaling pathway such as insulin receptor alpha and beta and insulin receptor substrate-1 were also involved. Accordingly, we speculate that the interaction of HDAC2 and insulin signaling system in PSGNs observed in the present study may serve as a potential mechanism in memory formation. We hope this could provide a valuable basis for understanding the roles of HDAC2 and insulin on cognitive impairment of diabetes mellitus, involved Alzheimer’s disease, which is also called type 3 diabetes recently. And this will also benefit to the treatment of insulin-related diseases in the central nervous system.

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.

Fig. 1

Similar content being viewed by others

References

  • Baskin DG, Sipols AJ, Schwartz MW, White MF (1993) Immunocytochemical detection of insulin receptor substrate-1 (IRS-1) in rat brain: colocalization with phosphotyrosine. Regul Pept 48:257–266

    Article  PubMed  CAS  Google Scholar 

  • Brands AM, Biessels GJ, de Haan EH, Kappelle LJ, Kessels RP (2005) The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care 28:726–735

    Article  PubMed  Google Scholar 

  • Broide RS, Redwine JM, Aftahi N, Young W, Bloom FE, Winrow CJ (2007) Distribution of histone deacetylases 1–11 in the rat brain. J Mol Neurosci 31:47–58

    Article  PubMed  CAS  Google Scholar 

  • Castillo-Quan JI (2009) Rosiglitazone effects to ameliorate Alzheimer’s disease pathogenic features: insulin signaling and neurotrophic factors. J Neuropsychiatr Clin Neurosci 21:347–348

    Article  Google Scholar 

  • Cheng D, Noble J, Tang MX, Schupf N, Mayeux R, Luchsinger JA (2011) Type 2 diabetes and late-onset Alzheimer’s disease. Dement Geriatr Cogn Disord 31:424–430

    Article  PubMed  CAS  Google Scholar 

  • Di Luca M, Ruts L, Gardoni F, Cattabeni F, Biessels GJ, Gispen WH (1999) NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats. Diabetologia 42:693–701

    Article  PubMed  Google Scholar 

  • Francis YI, Fa M, Ashraf H, Zhang H, Staniszewski A, Latchman DS, Arancio O (2009) Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer’s disease. J Alzheimers Dis 18:131–139

    PubMed  CAS  Google Scholar 

  • Gardoni F, Kamal A, Bellone C, Biessels GJ, Ramakers GM, Cattabeni F, Gispent WH, Di Luca M (2002) Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats. J Neurochem 80:438–447

    Article  PubMed  CAS  Google Scholar 

  • Gerrow K, Romorini S, Nabi SM, Colicos MA, Sala C, El-Husseini A (2006) A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 49:547–562

    Article  PubMed  CAS  Google Scholar 

  • Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60

    Article  PubMed  CAS  Google Scholar 

  • Hassing LB, Grant MD, Hofer SM, Pedersen NL, Nilsson SE, Berg S, McClearn G, Johansson B (2004) Type 2 diabetes mellitus contributes to cognitive decline in old age: a longitudinal population-based study. J Int Neuropsychol Soc 10:599–607

    Article  PubMed  Google Scholar 

  • Johnstone RW (2002) Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov 1:287–299

    Article  PubMed  CAS  Google Scholar 

  • Jolivalt CG, Hurford R, Lee CA, Dumaop W, Rockenstein E, Masliah E (2010) Type 1 diabetes exaggerates features of Alzheimer’s disease in APP transgenic mice. Exp Neurol 223:422–431

    Article  PubMed  CAS  Google Scholar 

  • Kaiser C, James SR (2004) Acetylation of insulin receptor substrate-1 is permissive for tyrosine phosphorylation. BMC Biol 2:23

    Article  PubMed  Google Scholar 

  • Kamal A, Biessels GJ, Urban IJ, Gispen WH (1999) Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. Neuroscience 90:737–745

    Article  PubMed  CAS  Google Scholar 

  • Kamal A, Ramakers GM, Gispen WH, Biessels GJ (2012) Effect of chronic intracerebroventricular insulin administration in rats on the peripheral glucose metabolism and synaptic plasticity of CA1 hippocampal neurons. Brain Res 1435:99–104

    Article  PubMed  CAS  Google Scholar 

  • Kania G, Blyszczuk P, Wobus AM (2004) The generation of insulin-producing cells from embryonic stem cells—a discussion of controversial findings. Int J Dev Biol 48:1061–1064

    Article  PubMed  Google Scholar 

  • Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, Sweatt JD, Rumbaugh G (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 

  • Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56

    Article  PubMed  CAS  Google Scholar 

  • Li F, Tsien JZ (2009) Memory and the NMDA receptors. N Engl J Med 361:302–303

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2011) Deficient brain insulin signalling pathway in Alzheimer’s disease and diabetes. J Pathol 225:54–62

    Article  PubMed  CAS  Google Scholar 

  • MacDonald JF, Jackson MF, Beazely MA (2006) Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. Crit Rev Neurobiol 18:71–84

    Article  PubMed  CAS  Google Scholar 

  • Malenka RC (2003) The long-term potential of LTP. Nat Rev Neurosci 4:923–926

    Article  PubMed  CAS  Google Scholar 

  • Mihaylova MM, Vasquez DS, Ravnskjaer K, Denechaud PD, Yu RT, Alvarez JG, Downes M, Evans RM, Montminy M, Shaw RJ (2011) Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell 145:607–621

    Article  PubMed  CAS  Google Scholar 

  • Mosley AL, Ozcan S (2004) The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose. J Biol Chem 279:54241–54247

    Article  PubMed  CAS  Google Scholar 

  • Nerup J, Pociot F (2001) A genomewide scan for type 1-diabetes susceptibility in Scandinavian families: identification of new loci with evidence of interactions. Am J Hum Genet 69:1301–1313

    Article  PubMed  CAS  Google Scholar 

  • Nooyens AC, Baan CA, Spijkerman AM, Verschuren WM (2010) Type 2 diabetes and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study. Diabetes Care 33:1964–1969

    Article  PubMed  Google Scholar 

  • Pessin JE, Saltiel AR (2000) Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest 106:165–169

    Article  PubMed  CAS  Google Scholar 

  • Plum L, Schubert M, Bruning JC (2005) The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 16:59–65

    Article  PubMed  CAS  Google Scholar 

  • Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S (2008) Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70:440–448

    Article  PubMed  CAS  Google Scholar 

  • Ronnemaa E, Zethelius B, Sundelof J, Sundstrom J, Degerman-Gunnarsson M, Berne C, Lannfelt L, Kilander L (2008) Impaired insulin secretion increases the risk of Alzheimer disease. Neurology 71:1065–1071

    Article  PubMed  CAS  Google Scholar 

  • Shibasaki M, Mizuno K, Kurokawa K, Ohkuma S (2011) Enhancement of histone acetylation in midbrain of mice with ethanol physical dependence and its withdrawal. Synapse 65:1244–1250

    Article  PubMed  CAS  Google Scholar 

  • Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—Is this type 3 diabetes? J Alzheimers Dis 7:63–80

    PubMed  CAS  Google Scholar 

  • Sun C, Zhou J (2008) Trichostatin A improves insulin stimulated glucose utilization and insulin signaling transduction through the repression of HDAC2. Biochem Pharmacol 76:120–127

    Article  PubMed  CAS  Google Scholar 

  • Susick L, Senanayake T, Veluthakal R, Woster PM, Kowluru A (2009) A novel histone deacetylase inhibitor prevents IL-1beta induced metabolic dysfunction in pancreatic beta-cells. J Cell Mol 13:1877–1885

    Article  Google Scholar 

  • Takigawa-Imamura H, Sekine T, Murata M, Takayama K, Nakazawa K, Nakagawa J (2003) Stimulation of glucose uptake in muscle cells by prolonged treatment with scriptide, a histone deacetylase inhibitor. Biosci Biotechnol Biochem 67:1499–1506

    Article  PubMed  CAS  Google Scholar 

  • Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE (2012) Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122:1316–1338

    Article  PubMed  CAS  Google Scholar 

  • van der Heide LP, Kamal A, Artola A, Gispen WH, Ramakers GM (2005) Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner. J Neurochem 94:1158–1166

    Article  PubMed  Google Scholar 

  • Wang YT, Salter MW (1994) Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature 369:233–235

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Lv Z, Hu Z, Sheng J, Hui B, Sun J, Ma L (2010) Chronic cocaine-induced H3 acetylation and transcriptional activation of CaMKIIalpha in the nucleus accumbens is critical for motivation for drug reinforcement. Neuropsychopharmacology 35:913–928

    Article  PubMed  CAS  Google Scholar 

  • Watson GS, Craft S (2003) The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs 17:27–45

    Article  PubMed  CAS  Google Scholar 

  • Whitehead JP, Clark SF, Urso B, James DE (2000) Signalling through the insulin receptor. Curr Opin Cell Biol 12:222–228

    Article  PubMed  CAS  Google Scholar 

  • Xiang K, Wang Y, Zheng T, Jia W, Li J, Chen L, Shen K, Wu S, Lin X, Zhang G, Wang C, Wang S, Lu H, Fang Q, Shi Y, Zhang R, Xu J, Weng Q (2004) Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21–q23 and chromosome 1q21–q24. Diabetes 53:228–234

    Article  PubMed  CAS  Google Scholar 

  • Yao ZG, Zhang L, Huang L, Zhu H, Liu Y, Ma CM, Sheng SL, Qin C (2012) Regional and cell-type specific distribution of HDAC2 in the adult mouse brain. Brain Struct Funct. doi:10.1007/s00429-012-0416-3

    PubMed  Google Scholar 

  • Zhao W, Chen H, Xu H, Moore E, Meiri N, Quon MJ, Alkon DL (1999) Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J Biol Chem 274:34893–34902

    Article  PubMed  CAS  Google Scholar 

  • Zhao HW, Christian SL, Castillo MR, Bult-Ito A, Drew KL (2006) Distribution of NMDA receptor subunit NR1 in arctic ground squirrel central nervous system. J Chem Neuroanat 32:196–207

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Doctorial Innovation Fund of Peking Union Medical College (2010-1001-001).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chuan Qin.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 39 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, ZG., Liu, Y., Zhang, L. et al. Co-location of HDAC2 and Insulin Signaling Components in the Adult Mouse Hippocampus. Cell Mol Neurobiol 32, 1337–1342 (2012). https://doi.org/10.1007/s10571-012-9859-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-012-9859-6

Keywords

Navigation