Skip to main content

Advertisement

SpringerLink
Log in

Inhibitory Effect of Memantine on Streptozotocin-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Neurotrophic Factor Decline in Astrocytes

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Our earlier studies showed that insulin receptor (IR) dysfunction along with neuroinflammation and amyloidogenesis played a major role in streptozotocin (STZ)-induced toxicity in astrocytes. N-methyl-D-aspartate (NMDA) receptor antagonist-memantine shows beneficial effects in Alzheimer’s disease (AD) pathology. However, the protective molecular and cellular mechanism of memantine in astrocytes is not properly understood. Therefore, the present study was undertaken to investigate the effect of memantine on insulin receptors, neurotrophic factors, neuroinflammation, and amyloidogenesis in STZ-treated astrocytes. STZ (100 μM) treatment for 24 h in astrocytes resulted significant decrease in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and insulin-degrading enzyme (IDE) expression in astrocytes. Treatment with memantine (1–10 μM) improved STZ-induced neurotrophic factor decline (BDNF, GDNF) along with IR dysfunction as evidenced by a significant increase in IR protein expression, phosphorylation of IRS-1, Akt, and GSK-3 α/β in astrocytes. Further, memantine attenuated STZ-induced amyloid precursor protein (APP), β-site APP-cleaving enzyme-1 and amyloid-β1–42 expression and restored IDE expression in astrocytes. In addition, memantine also displays protective effects against STZ-induced astrocyte activation showed by reduction of inflammatory markers, nuclear factor kappa-B translocation, glial fibrillary acidic protein, cyclooxygenase-2, tumor necrosis factor-α level, and oxidative-nitrostative stress. The results suggest that besides the NMDA receptor antagonisic activity, effect on astroglial IR and neurotrophic factor may also be an important factor in the beneficial effect of memantine in AD pathology.

Novel neuroprotective mechanisms of memenatine in streptozotocin-induced toxicity in astrocytes

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

Access this article

Log in via an institution

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
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2(12):679–689

    Article  CAS  PubMed  Google Scholar 

  2. Halassa MM, Haydon PG (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol 72:335–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Henneberger C, Papouin T, Oliet SH, Rusakov DA (2010) Long-term potentiation depends on release of D-serine from astrocytes. Nature 463(7278):232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32(8):421–431

    Article  CAS  PubMed  Google Scholar 

  5. Desagher S, Glowinski J, Premont J (1996) Astrocytes protect neurons from hydrogen peroxide toxicity. J Neurosci 16(8):2553–2562

    CAS  PubMed  Google Scholar 

  6. Chen LW, Yung KL, Chan YS (2005) Reactive astrocytes as potential manipulation targets in novel cell replacement therapy of Parkinson’s disease. Curr Drug Targets 6(7):821–833

    Article  CAS  PubMed  Google Scholar 

  7. Chen PS, Peng GS, Li G, Yang S, Wu X, Wang CC, Wilson B, Lu RB et al (2006) Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry 11(12):1116–1125

    Article  CAS  PubMed  Google Scholar 

  8. Yeh CW, Yeh SH, Shie FS, Lai WS, Liu HK, Tzeng TT, Tsay HJ, Shiao YJ (2015) Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice. Neurobiol Aging.

  9. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119(1):7–35

    Article  PubMed  Google Scholar 

  10. Rajasekar N, Dwivedi S, Tota SK, Kamat PK, Hanif K, Nath C, Shukla R (2013) Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice. Eur J Pharmacol 715(1-3):381–394

    Article  CAS  PubMed  Google Scholar 

  11. Agrawal R, Tyagi E, Shukla R, Nath C (2011) Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol 21(3):261–273

    Article  CAS  PubMed  Google Scholar 

  12. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR et al (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(1):63–80

    CAS  PubMed  Google Scholar 

  13. Simpson JE, Ince PG, Shaw PJ, Heath PR, Raman R, Garwood CJ, Gelsthorpe C, Baxter L et al (2011) Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer’s pathology and APOE genotype. Neurobiol Aging 32(10):1795–1807

    Article  CAS  PubMed  Google Scholar 

  14. Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296(5573):1655–1657

    Article  CAS  PubMed  Google Scholar 

  15. Wang X, Zheng W, Xie JW, Wang T, Wang SL, Teng WP, Wang ZY (2010) Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model. Mol Neurodegener 5:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Barilar JO, Knezovic A, Grunblatt E, Riederer P, Salkovic-Petrisic M (2015) Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer’s disease. J Neural Transm 122(4):565–576

    Article  CAS  PubMed  Google Scholar 

  17. Yang LB, Lindholm K, Yan R, Citron M, Xia W, Yang XL, Beach T, Sue L et al (2003) Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat Med 9(1):3–4

    Article  CAS  PubMed  Google Scholar 

  18. Frisardi V, Solfrizzi V, Imbimbo PB, Capurso C, D’Introno A, Colacicco AM, Vendemiale G, Seripa D et al (2010) Towards disease-modifying treatment of Alzheimer’s disease: drugs targeting beta-amyloid. Curr Alzheimer Res 7(1):40–55

    Article  CAS  PubMed  Google Scholar 

  19. Alley GM, Bailey JA, Chen D, Ray B, Puli LK, Tanila H, Banerjee PK, Lahiri DK (2010) Memantine lowers amyloid-beta peptide levels in neuronal cultures and in APP/PS1 transgenic mice. J Neurosci Res 88(1):143–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Biswas A, Kurkute P, Saleem S, Jana B, Mohapatra S, Mondal P, Adak A, Ghosh S et al (2015) Novel Hexapeptide Interacts with Tubulin and Microtubules, Inhibits Abeta Fibrillation, and Shows Significant Neuroprotection. ACS Chem Neurosci 6(8):1309–1316

    Article  CAS  PubMed  Google Scholar 

  21. Wang Y, Li M, Tang J, Song M, Xu X, Xiong J, Li J, Bai Y (2011) Glucocorticoids facilitate astrocytic amyloid-beta peptide deposition by increasing the expression of APP and BACE1 and decreasing the expression of amyloid-beta-degrading proteases. Endocrinology 152(7):2704–2715

    Article  CAS  PubMed  Google Scholar 

  22. Rajasekar N, Dwivedi S, Nath C, Hanif K, Shukla R (2014) Protection of streptozotocin induced insulin receptor dysfunction, neuroinflammation and amyloidogenesis in astrocytes by insulin. Neuropharmacology 86:337–352

    Article  CAS  PubMed  Google Scholar 

  23. Akiyama H, Mori H, Saido T, Kondo H, Ikeda K, McGeer PL (1999) Occurrence of the diffuse amyloid beta-protein (Abeta) deposits with numerous Abeta-containing glial cells in the cerebral cortex of patients with Alzheimer’s disease. Glia 25(4):324–331

    Article  CAS  PubMed  Google Scholar 

  24. Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A (2009) Astroglia in dementia and Alzheimer’s disease. Cell Death Differ 16(3):378–385

    Article  CAS  PubMed  Google Scholar 

  25. Saido TC (1998) Alzheimer’s disease as proteolytic disorders: anabolism and catabolism of beta-amyloid. Neurobiol Aging 19(1 Suppl):S69–S75

    Article  CAS  PubMed  Google Scholar 

  26. Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE et al (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100(7):4162–4167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Heni M, Hennige AM, Peter A, Siegel-Axel D, Ordelheide AM, Krebs N, Machicao F, Fritsche A et al (2011) Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLoS ONE 6(6):e21594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ (2003) Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 348(14):1333–1341

    Article  CAS  PubMed  Google Scholar 

  29. Wu HM, Tzeng NS, Qian L, Wei SJ, Hu X, Chen SH, Rawls SM, Flood P et al (2009) Novel neuroprotective mechanisms of memantine: increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation. Neuropsychopharmacology 34(10):2344–2357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kamat PK, Rai S, Swarnkar S, Shukla R, Ali S, Najmi AK, Nath C (2013) Okadaic acid-induced Tau phosphorylation in rat brain: role of NMDA receptor. Neuroscience 238:97–113

    Article  CAS  PubMed  Google Scholar 

  31. Rai S, Kamat PK, Nath C, Shukla R (2013) A study on neuroinflammation and NMDA receptor function in STZ (ICV) induced memory impaired rats. J Neuroimmunol 254(1-2):1–9

    Article  CAS  PubMed  Google Scholar 

  32. Lipton SA (2007) Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation. Curr Drug Targets 8(5):621–632

    Article  CAS  PubMed  Google Scholar 

  33. Zhao X, Marszalec W, Toth PT, Huang J, Yeh JZ, Narahashi T (2006) In vitro galantamine-memantine co-application: mechanism of beneficial action. Neuropharmacology 51(7-8):1181–1191

    Article  CAS  PubMed  Google Scholar 

  34. Arif M, Chikuma T, Ahmed MM, Nakazato M, Smith MA, Kato T (2009) Effects of memantine on soluble Alphabeta(25-35)-induced changes in peptidergic and glial cells in Alzheimer’s disease model rat brain regions. Neuroscience 164(3):1199–1209

    Article  CAS  PubMed  Google Scholar 

  35. Niranjan R, Rajasekar N, Nath C, Shukla R (2012) The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6. Chem Biol Interact 200(2-3):73–83

    Article  CAS  PubMed  Google Scholar 

  36. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  37. Tiwari RL, Singh V, Singh A, Barthwal MK (2011) IL-1R-associated kinase-1 mediates protein kinase Cdelta-induced IL-1beta production in monocytes. J Immunol 187(5):2632–2645

    Article  CAS  PubMed  Google Scholar 

  38. Niranjan R, Nagarajan R, Hanif K, Nath C, Shukla R (2014) LPS induces mediators of neuroinflammation, cell proliferation, and GFAP expression in human astrocytoma cells U373MG: the anti-inflammatory and anti-proliferative effect of guggulipid. Neurol Sci 35(3):409–414

    Article  PubMed  Google Scholar 

  39. Chadwick W, Mitchell N, Caroll J, Zhou Y, Park SS, Wang L, Becker KG, Zhang Y et al (2011) Amitriptyline-mediated cognitive enhancement in aged 3xTg Alzheimer’s disease mice is associated with neurogenesis and neurotrophic activity. PLoS ONE 6(6):e21660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Revilla S, Ursulet S, Alvarez-Lopez MJ, Castro-Freire M, Perpina U, Garcia-Mesa Y, Bortolozzi A, Gimenez-Llort L et al (2014) Lenti-GDNF gene therapy protects against Alzheimer’s disease-like neuropathology in 3xTg-AD mice and MC65 cells. CNS Neurosci Ther 20(11):961–972

    Article  CAS  PubMed  Google Scholar 

  41. Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 7(5):695–702

    Article  CAS  PubMed  Google Scholar 

  42. Konishi Y, Yang LB, He P, Lindholm K, Lu B, Li R, Shen Y (2014) Deficiency of GDNF Receptor GFRalpha1 in Alzheimer’s Neurons Results in Neuronal Death. J Neurosci 34(39):13127–13138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sim YJ (2014) Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer’s disease rats. J Exerc Rehabil 10(2):81–88

    Article  PubMed  PubMed Central  Google Scholar 

  44. Marvanova M, Lakso M, Pirhonen J, Nawa H, Wong G, Castren E (2001) The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci 18(3):247–258

    Article  CAS  PubMed  Google Scholar 

  45. Caumont AS, Octave JN, Hermans E (2006) Amantadine and memantine induce the expression of the glial cell line-derived neurotrophic factor in C6 glioma cells. Neurosci Lett 394(3):196–201

    Article  CAS  PubMed  Google Scholar 

  46. Chu JM, Lee DK, Wong DP, Wong RN, Yung KK, Cheng CH, Yue KK (2014) Ginsenosides attenuate methylglyoxal-induced impairment of insulin signaling and subsequent apoptosis in primary astrocytes. Neuropharmacology 85:215–223

    Article  CAS  PubMed  Google Scholar 

  47. Ang LC, Bhaumick B, Munoz DG, Sass J, Juurlink BH (1992) Effects of astrocytes, insulin and insulin-like growth factor I on the survival of motoneurons in vitro. J Neurol Sci 109(2):168–172

    Article  CAS  PubMed  Google Scholar 

  48. Craft S (2006) Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications. Alzheimer Dis Assoc Disord 20(4):298–301

    Article  CAS  PubMed  Google Scholar 

  49. Tsuchida A, Nakagawa T, Itakura Y, Ichihara J, Ogawa W, Kasuga M, Taiji M, Noguchi H (2001) The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice. Diabetologia 44(5):555–566

    Article  CAS  PubMed  Google Scholar 

  50. Yamada M, Ohnishi H, Sano S, Nakatani A, Ikeuchi T, Hatanaka H (1997) Insulin receptor substrate (IRS)-1 and IRS-2 are tyrosine-phosphorylated and associated with phosphatidylinositol 3-kinase in response to brain-derived neurotrophic factor in cultured cerebral cortical neurons. J Biol Chem 272(48):30334–30339

    Article  CAS  PubMed  Google Scholar 

  51. Agrawal R, Mishra B, Tyagi E, Nath C, Shukla R (2010) Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat. Pharmacol Res 61(3):247–252. doi:10.1016/j.phrs.2009.12.008

    Article  CAS  PubMed  Google Scholar 

  52. Agrawal R, Tyagi E, Shukla R, Nath C (2009) A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia. Neuropharmacology 56(4):779–787

    Article  CAS  PubMed  Google Scholar 

  53. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378(6559):785–789

    Article  CAS  PubMed  Google Scholar 

  54. Ponce-Lopez T, Liy-Salmeron G, Hong E, Meneses A (2011) Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3beta decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Res 1426:73–85

    Article  CAS  PubMed  Google Scholar 

  55. De Sarno P, Bijur GN, Zmijewska AA, Li X, Jope RS (2006) In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors. Neurobiol Aging 27(3):413–422

    Article  CAS  PubMed  Google Scholar 

  56. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW (2004) Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci U S A 101(7):2173–2178

    Article  CAS  PubMed  Google Scholar 

  57. Phiel CJ, Wilson CA, Lee VM, Klein PS (2003) GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 423(6938):435–439

    Article  CAS  PubMed  Google Scholar 

  58. Ly PT, Wu Y, Zou H, Wang R, Zhou W, Kinoshita A, Zhang M, Yang Y et al (2013) Inhibition of GSK3beta-mediated BACE1 expression reduces Alzheimer-associated phenotypes. J Clin Invest 123(1):224–235

    Article  CAS  PubMed  Google Scholar 

  59. Zhao J, O’Connor T, Vassar R (2011) The contribution of activated astrocytes to Abeta production: implications for Alzheimer’s disease pathogenesis. J Neuroinflammation 8:150

    Article  CAS  PubMed  Google Scholar 

  60. Leuba G, Wernli G, Vernay A, Kraftsik R, Mohajeri MH, Saini KD (2005) Neuronal and nonneuronal quantitative BACE immunocytochemical expression in the entorhinohippocampal and frontal regions in Alzheimer’s disease. Dement Geriatr Cogn Disord 19(4):171–183

    Article  CAS  PubMed  Google Scholar 

  61. Pizzi M, Boroni F, Bianchetti A, Moraitis C, Sarnico I, Benarese M, Goffi F, Valerio A et al (2002) Expression of functional NR1/NR2B-type NMDA receptors in neuronally differentiated SK-N-SH human cell line. Eur J Neurosci 16(12):2342–2350

    Article  PubMed  Google Scholar 

  62. Okamoto S, Sherman K, Lipton SA (1999) Absence of binding activity of neuron-restrictive silencer factor is necessary, but not sufficient for transcription of NMDA receptor subunit type 1 in neuronal cells. Brain Res Mol Brain Res 74(1-2):44–54

    Article  CAS  PubMed  Google Scholar 

  63. Lipton SA (2004) Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx 1(1):101–110

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hostetler KY, Richman DD (1982) Studies on the mechanism of phospholipid storage induced by amantadine and chloroquine in Madin Darby canine kidney cells. Biochem Pharmacol 31(23):3795–3799

    Article  CAS  PubMed  Google Scholar 

  65. Honegger UE, Quack G, Wiesmann UN (1993) Evidence for lysosomotropism of memantine in cultured human cells: cellular kinetics and effects of memantine on phospholipid content and composition, membrane fluidity and beta-adrenergic transmission. Pharmacol Toxicol 73(4):202–208

    Article  CAS  PubMed  Google Scholar 

  66. Caccamo A, Oddo S, Sugarman MC, Akbari Y, LaFerla FM (2005) Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol Aging 26(5):645–654

    Article  CAS  PubMed  Google Scholar 

  67. Miller BC, Eckman EA, Sambamurti K, Dobbs N, Chow KM, Eckman CB, Hersh LB, Thiele DL (2003) Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivo. Proc Natl Acad Sci U S A 100(10):6221–6226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mulder SD, Veerhuis R, Blankenstein MA, Nielsen HM (2012) The effect of amyloid associated proteins on the expression of genes involved in amyloid-beta clearance by adult human astrocytes. Exp Neurol 233(1):373–379

    Article  CAS  PubMed  Google Scholar 

  69. Shingo AS, Kanabayashi T, Murase T, Kito S (2012) Cognitive decline in STZ-3V rats is largely due to dysfunctional insulin signalling through the dentate gyrus. Behav Brain Res 229(2):378–383

    Article  CAS  PubMed  Google Scholar 

  70. Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, Sun X, Frosch MP, Selkoe DJ (2003) Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40(6):1087–1093

    Article  CAS  PubMed  Google Scholar 

  71. Shingo AS, Kanabayashi T, Kito S, Murase T (2013) Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. Behav Brain Res 241:105–111

    Article  CAS  PubMed  Google Scholar 

  72. Bedse G, Di Domenico F, Serviddio G, Cassano T (2015) Aberrant insulin signaling in Alzheimer’s disease: current knowledge. Front Neurosci 9:204

    Article  PubMed  PubMed Central  Google Scholar 

  73. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318

    Article  CAS  PubMed  Google Scholar 

  74. Rossi DJ, Brady JD, Mohr C (2007) Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10(11):1377–1386

    Article  CAS  PubMed  Google Scholar 

  75. Swarnkar S, Singh S, Goswami P, Mathur R, Patro IK, Nath C (2012) Astrocyte activation: a key step in rotenone induced cytotoxicity and DNA damage. Neurochem Res 37(10):2178–2189

    Article  CAS  PubMed  Google Scholar 

  76. Niranjan R, Nath C, Shukla R (2011) Guggulipid and nimesulide differentially regulated inflammatory genes mRNA expressions via inhibition of NF-kB and CHOP activation in LPS-stimulated rat astrocytoma cells, C6. Cell Mol Neurobiol 31(5):755–764

    Article  CAS  PubMed  Google Scholar 

  77. Kashon ML, Ross GW, O’Callaghan JP, Miller DB, Petrovitch H, Burchfiel CM, Sharp DS, Markesbery WR et al (2004) Associations of cortical astrogliosis with cognitive performance and dementia status. J Alzheimers Dis 6(6):595–604, discussion 673-581

    PubMed  Google Scholar 

Download references

Acknowledgments

Financial support from DBT (BT/PR4012/MED/30/672/201 Dated 28/03/2012) and SRF to Rajasekar N from CSIR, New Delhi, India, are gratefully acknowledged. Authors are also thankful to Dr. A.K. Balapure and their team for providing rat astrocytoma cell line (C6).

Conflict of Interest

There is no conflict of interest among any of the contributing authors.

Author information

Authors and Affiliations

  1. Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226031, India

    N. Rajasekar, Chandishwar Nath, Kashif Hanif & Rakesh Shukla

  2. Academy of Scientific and Innovative Research (AcSIR), Chennai, India

    N. Rajasekar, Chandishwar Nath, Kashif Hanif & Rakesh Shukla

Authors
  1. N. Rajasekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chandishwar Nath
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kashif Hanif
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rakesh Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rakesh Shukla.

Additional information

This article is in accordance with CSIR-CDRI communication no: 9141

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rajasekar, N., Nath, C., Hanif, K. et al. Inhibitory Effect of Memantine on Streptozotocin-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Neurotrophic Factor Decline in Astrocytes. Mol Neurobiol 53, 6730–6744 (2016). https://doi.org/10.1007/s12035-015-9576-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9576-5

Keywords

Search

Navigation