Skip to main content

Advertisement

SpringerLink
Log in

Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

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
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  • Ahmad A, Shah SA, Badshah H, Kim MJ, Ali T, Yoon GH, Kim TH, Abid NB, Rehman SU, Khan S, Kim MO (2016) Neuroprotection by vitamin C against ethanol-induced neuroinflammation associated neurodegeneration in the developing rat brain. CNS Neurol Disord Drug Targets 15:360–370

    Article  CAS  PubMed  Google Scholar 

  • Bensimon G, Chermat R (1991) Microtubule disruption and cognitive defects: effect of colchicine on learning behavior in rats. Pharmacol Biochem Behav 38:141–145

    Article  CAS  PubMed  Google Scholar 

  • Bland JS (1998) The pro oxidant and anti-oxidant effects of vitamin C. Alternatv Med Rev 3:170–173

    CAS  Google Scholar 

  • Britschgi M, Wyss-Coray T (2007) Systemic and acquired immune responses, in Alzheimer’s disease. Int Rev Neurobiol 82:205–233

    Article  CAS  PubMed  Google Scholar 

  • Carr A, Frei B (1999) Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J 13:1007–1024

    CAS  PubMed  Google Scholar 

  • Chakraborthy A, Ramani P, Sherlin HJ, Premkumar P, Natesan A (2014) Antioxidant and pro-oxidant activity of vitamin C in oral environment.Indian. J Dent Res 25:499–504

    Google Scholar 

  • Coşkun Ş, Gönül B, Güzel NA, Balabanlí B (2005) The effects of vitamin C supplementation on oxidative stress and antioxidant content in the brains of chronically exercised rats. Mol Cell Biochem 280:135–138

    Article  CAS  PubMed  Google Scholar 

  • Cox G (1977) Neuropathological techniques. In: Bancroft JD, Stevens A (eds) Theory & Practice of histological techniques. Elsevier, London, pp. 258–259

    Google Scholar 

  • Csolle C, Sperlagh B (2010). Peripheral origin of IL-1β production in the rodent hippocampus under invivo systemic bacterial lipoplysaccharide (LPS) challenge and it’s regulation by P2X7 receptors. J Neuroimmunol 219: 38–46.

  • Csölle C, Sperlagh B (2011) Endo-cannabinergic modulation of IL-1β in mouse hippo-campus under basal conditions and after in vivo systemic lipopolysaccharide stimulation. Neuroimmunomodulation 18:226–231

    Article  CAS  PubMed  Google Scholar 

  • Emerich DF, Walsh TJ (1990) Cholinergic cell loss and cognitive impairments following intraventricular or intradentate injection of colchicine. Brain Res 517:157–167

    Article  CAS  PubMed  Google Scholar 

  • Garg MC, Bansal DD (2000) Protective antioxidant effect of vitamins in streptozotocin induced stress in diabetic rats. Indian J ExpBiol 38:101–104

    CAS  Google Scholar 

  • Gehrmann J, Matsumoto Y, Kreutzberg GW (1995) Microglia: intrinsic immune effector cell of the brain. Brain Res Rev 20:269–287

    Article  CAS  PubMed  Google Scholar 

  • Goswami AR, Dutta G, Ghosh T (2014) Effects of vitamin C on the hypobaric hypoxia-induced immune changes in male rats. Int J Biometeorol 58:1961–1971

    Article  PubMed  Google Scholar 

  • Goulding NJ, Flower RJ (1993) Glucocorticoids and the immune system. In: Buckingham, JC, Gillies GE, Cowell a (eds), stress, stress hormone and the immune system. Wiley, New York. J MagnResonImaging 32:383–387

    Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  • Hansen SN, Nyborg PT, Lykkesfeldt J (2014) Does vitamin C deficiency affect cognitive development and function? Nutrients 6:3818–3846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Justo GZ, Duran N, Queiroz MLS (2000) Myelopoietic response in tumor-bearing mice by an aggregated polymer isolated from Aspergillus oryzae. Eur J Pharmacol 388:219–226

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Seghal N, Padi SSV (2006) Naidu PS. Differential effects of cyclooxygenase inhibitors on intracerebroventricular colchicine-induced dysfunction and oxidative stress in rats: European Journal of Pharmacology 551:58–66

    CAS  PubMed  Google Scholar 

  • Kumar A, Naidu PS, Seghal N, Padi SSV, Goyal R (2007) Colchicine induced neurotoxicity as an animal model of sporadic dementia of Alzheimer’s type. PharmRep 59:274–283

    CAS  Google Scholar 

  • Lawal RA, Ozaslan MD, Odesanmi OS, Karagoz ID, Kilic IH, Ebuehi OAT (2013) Cytotoxic and antiproliferative activity of Securidacalongepedunculataaqueous extract on Ehrlich ascitescarcinoma cells in Swiss albino mice. International Journal of Applied Research in Natural Products 5:19–27

    Google Scholar 

  • Lehr HA, Frei B, Arfors KE (1994) Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo (platelets/vitamn E/probucol/hamster/intravitalmiroscopy). Proc Natl Acad Sci U S A 91:7688–7692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J BiolChem 193:265–275

    CAS  Google Scholar 

  • Lü JM, Lin PH, Yao Q, Chen C (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14:840–860

    Article  CAS  PubMed  Google Scholar 

  • Mallat M, Chamak B (1994) Brain macrophages: neurotoxic or neurotrophic effector cells? J LeukocBiol 56:416–422

    CAS  Google Scholar 

  • Maluish AE, Halliday WJ (1979) Hemocytometer leukocyte adherence technique. Cancer Res 39:625–626

    CAS  PubMed  Google Scholar 

  • Mikirova NA (2007) The effect of high dose IV vitamin C on plasma antioxidant capacity and level of oxidative stress in cancer patients and healthy subjects. J Orthomol Med 22:3

    Google Scholar 

  • Mikirova N, Casciari J, Rogers A, Taylor P (2012) Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J Transl Med 10:189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizuno M, Yamada K, Olariu A, Nawa H, Nabeshima T (2000) Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J Neurosci 20:7116–7121

    CAS  PubMed  Google Scholar 

  • Nakayama T, Sawada T (2002) Involvement of microtubule integrity in memory impairment caused by colchicine. Pharmacology, Biochemistry & Behavior 71:119–138

    Article  CAS  Google Scholar 

  • Oben JA, Foreman JC (1988) A simple quantitative fluorimetric assay of in vitro phagocytocis in human neutrophils. J Immunol Methods 112:99–103

  • Paxinos G, Watson C (1986) The Rat Brain in Stereotaxic Coordinates. Academic Press, San Diego.

  • Pitchaimani V, Arumugam S, Thandavarayan RA, Thiyagarajan MK, Aiyalu R, Sreedhar R, Nakamura T, Watanabe JK (2012) Nootropic activityof acetaminophen against colchicine induced cognitive impairment in rats. Journal of Clinical Biochemistry & Nutrition 50:241–244

    Article  CAS  Google Scholar 

  • 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 254:1–9

    Article  CAS  PubMed  Google Scholar 

  • Shah SA, Yoon GH, Kim HO, Kim MO (2015) Vitamin C neuroprotection against dose-dependent glutamate-induced neurodegeneration in the postnatal brain. Neurochem Res 40:875–884

    Article  CAS  PubMed  Google Scholar 

  • Shigematsu K, McGeer PL (1992). Accumulation of Amyloid Precursor Protein in Neurons after Intraventricular Injection of Coichicine. Am J Pathol 140: 787–794.

  • Sil S, Ghosh T (2016) Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer's disease. J Neuroimmunol 291:115–124

    Article  CAS  PubMed  Google Scholar 

  • Sil S, Goswami AR, Dutta G, Ghosh T (2014) Effects of naproxen on some immune responses in colchicine induced rat model of Alzheimer’s disease. Neuroimmunomodulat 21:304–321

    Article  CAS  Google Scholar 

  •  Sil S,  Ghosh A, Ghosh T K  (2016a) Impairment of blood brain barrier is related with the neuroinflammation induced peripheral immune status in intracerebroventricular colchicine injected rats: An experimental study with mannitol. Brain Research 1646:278–286

  • Sil S, Ghosh TK, Ghosh R (2016b) NMDA receptor is involved in neuroinflammation in intracerebroventricular colchicine-injected rats. J Immunotoxicol. doi:10.3109/1547691X.2015.1130760

  • Sil S, Ghosh R, Sanyal M, Guha D, Ghosh TK (2016c) A comparison of neurodegeneration linked with neuroinflammation in brain areas of rats after intracerebroventricular colchicine injection. J Immunotoxicol 13:182–190

  • Siripin D, Fucharoen S, Tanyong DI (2011) Nitric oxide and caspase 3 mediated cytokine induced apoptosis in acute leukemia. Asian Pac J Allergy Immunol 29:102–111

    CAS  PubMed  Google Scholar 

  • Socci DJ, Bjugstad KB, Jones HC, Pattisapu JV, Arendash GW (1999) Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model. Exp Neurol 155:109–117

    Article  CAS  PubMed  Google Scholar 

  • Stevens A, Bancroft JD (1977) (eds.). Proteins and nucleic acids. In: Theory and practice of histological techniques. Elsevier, London pp. 129

  • Tilson HA, Harry GJ, McLamb RL, Peterson NJ, Rodgers BC, Pedriaditakis P, Ali SF (1988) Role of dentate gyrus cells in retention of a radial arm maze task and sensitivity of rats to cholinergic drugs. BehavNeurosci 102:835–842

    CAS  Google Scholar 

  • Weidmann E, Brieger J, Jahn B, Hoelzer D, Bergmann L, Mitrou PS (1995) Lactate dehydrogenase-release assay: a reliable, nonradioactive technique for analysis of cytotoxic lymphocyte-mediated lytic activity against blasts from acute myelocytic leukemia. Ann Hematol 70:153–158

    Article  CAS  PubMed  Google Scholar 

  • Wilson L (1986) Microtubules as targets for drug and toxic chemical action: the mechanisms of colchicine and vinblastine. In: Clarkson TW, Sagar PR, Syversen TLM (eds) The cytoskeleton-a target for toxic agents. Plenum Press, New York, pp. 37–52

    Chapter  Google Scholar 

  • Xavier SM, Barbosa CO, Barros DO, Silva RF, Oliveira AA, Freitas RM (2007) Vitamin C antioxidant effects in hippocampus of adult Wistar rats after seizures and status epilepticus induced by pilocarpine. Neuroscience Letters 420:76–79

Download references

Acknowledgment

This research work was supported by the University Grant Commission - Major Research Project [F. No. 42-532/2013 (SR) dt. 22nd March, 2013]. Debajit Bhowmick [Nanoscience and Nanocentre, University of Calcutta] and Dr. Arijit Ghosh (post doc fellow in the Neurophysiology laboratory) are acknowledged for their assistances in some parts of the work.

Author information

Author notes

  1. Susmita Sil

    Present address: Department of Pharmacology and Experimental Neuroscience, Durham Research Center, UNMC, Omaha, NE, USA

Authors and Affiliations

  1. Neurophysiology laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata, West Bengal, 700 009, India

    Susmita Sil, Tusharkanti Ghosh, Pritha Gupta, Rupsa Ghosh & Avishek Roy

  2. Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, West Bengal, 700032, India

    Syed N Kabir

Authors
  1. Susmita Sil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tusharkanti Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pritha Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rupsa Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Syed N Kabir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Avishek Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tusharkanti Ghosh.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sil, S., Ghosh, T., Gupta, P. et al. Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease. J Mol Neurosci 60, 421–435 (2016). https://doi.org/10.1007/s12031-016-0817-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-016-0817-5

Keywords

Search

Navigation