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Curcumin Rescues Aging-Related Loss of Hippocampal Synapse Input Specificity of Long Term Potentiation in Mice

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Abstract

Curcumin has neuroprotective effect and could enhance memory. However, the mechanisms underlying the protection of curcumin on aging-related memory decline are not well understood. In this study, high frequency stimulation (HFS)-induced long term potentiation (LTP) was evaluated by a cellular model of memory formation. A two-input stimulation paradigm was used to record the potentiation as well as synapse input specificity. The data suggested that an N-Methyl-d-aspartate receptors (NMDAR) -dependent LTP was inducible in adult hippocampal slices with a characteristic of synapse input specificity. It also indicated that aging resulted in a reduction in LTP but more importantly a loss of synaptic input specificity. The reason behind the above conclusions is that LTP induction is more dependent on the calcium channel. This is due to a switch of the dependence of LTP induction to voltage-dependent calcium channel (VDCC) compared to NMDA receptors. Curcumin administration recovers input specificity by re-establishing NMDA receptor dependence of induction. In addition, curcumin administration ameliorated aging-related increase of brain thiobarbituric acid-reactive substances and elevated aging-related decrease of glutathione in hippocampus. It is then concluded that curcumin modulates hippocampal redox status and restores aging-related loss of synapse input specificity of HFS-induced LTP by switching VDCC calcium source into NMDA receptor-dependent one.

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Abbreviations

LTP:

Long term potentiation

ROS:

Reactive oxidative species

AD:

Alzheimer’s disease

HFS:

High frequency stimulation

NMDARs:

N-methyl-d-aspartate receptors

References

  1. Waite LM, Broe GA, Creasey H, Grayson DA, Cullen JS, O’Toole B, Edelbrock D, Dobson M (1997) Neurodegenerative and other chronic disorders among people aged 75 years and over in the community. Med J Aust 167:429–432

    PubMed  CAS  Google Scholar 

  2. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69:143–179

    Article  PubMed  CAS  Google Scholar 

  3. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  4. Bashir ZI, Alford S, Davies SN, Randall AD, Collingridge GL (1991) Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature 349:156–158

    Article  PubMed  CAS  Google Scholar 

  5. Nicoll RA, Malenka RC (1995) Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 377:115–118

    Article  PubMed  CAS  Google Scholar 

  6. Ris L, Godaux E (2007) Synapse specificity of long-term potentiation breaks down with aging. Learn Mem 14:185–189

    Article  PubMed  Google Scholar 

  7. Zhu G, Huang Y, Chen Y, Zhuang Y, Behnisch T (2012) MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors. J Neurochem. doi:10.1111/j.1471-4159.2012.07815.x

  8. Shishodia S, Sethi G, Aggarwal BB (2005) Curcumin: getting back to the roots. Ann NY Acad Sci 1056:206–217

    Article  PubMed  CAS  Google Scholar 

  9. Strimpakos AS, Sharma RA (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10:511–545

    Article  PubMed  CAS  Google Scholar 

  10. Tsai YM, Chien CF, Lin LC, Tsai TH (2011) Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm 416:331–338

    Article  PubMed  CAS  Google Scholar 

  11. Bala K, Tripathy BC, Sharma D (2006) Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology 7:81–89

    Article  PubMed  CAS  Google Scholar 

  12. Panchal HD, Vranizan K, Lee CY, Ho J, Ngai J, Timiras PS (2008) Early anti-oxidative and anti-proliferative curcumin effects on neuroglioma cells suggest therapeutic targets. Neurochem Res 33:1701–1710

    Article  PubMed  CAS  Google Scholar 

  13. Mythri RB, Bharath MM (2012) Curcumin: a potential neuroprotective agent in Parkinson’s disease. Curr Pharm Des 18:91–99

    Article  PubMed  CAS  Google Scholar 

  14. Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Ataee R, Moghaddam SN (2010) Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain. J Med Food 13:821–826

    Article  PubMed  CAS  Google Scholar 

  15. Daniel S, Limson JL, Dairam A, Watkins GM, Daya S (2004) Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem 98:266–275

    Article  PubMed  CAS  Google Scholar 

  16. Shen SQ, Zhang Y, Xiang JJ, Xiong CL (2007) Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes. World J Gastroenterol 13:1953–1961

    PubMed  CAS  Google Scholar 

  17. Sumanont Y, Murakami Y, Tohda M, Vajragupta O, Watanabe H, Matsumoto K (2007) Effects of manganese complexes of curcumin and diacetylcurcumin on kainic acid-induced neurotoxic responses in the rat hippocampus. Biol Pharm Bull 30:1732–1739

    Article  PubMed  CAS  Google Scholar 

  18. Zhu G, Chen Y, Huang Y, Li Q, Behnisch T (2011) MPTP-meditated hippocampal dopamine deprivation modulates synaptic transmission and activity-dependent synaptic plasticity. Toxicol Appl Pharmacol 254:332–341

    Article  PubMed  CAS  Google Scholar 

  19. Behnisch T, Wilsch VW, Balschun D, Reymann KG (1998) The role of group II metabotropic glutamate receptors in hippocampal CA1 long-term potentiation in vitro. Eur J Pharmacol 356:159–165

    Article  PubMed  CAS  Google Scholar 

  20. Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, Peng H, Aburaya J, Ishihara K, Sakanaka M (1997) Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root. Neurosci Res 28:191–200

    Article  PubMed  CAS  Google Scholar 

  21. Wu A, Ying Z, Schubert D, Gomez-Pinilla F (2011) Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma. Neurorehabil Neural Repair 25:332–342

    Article  PubMed  Google Scholar 

  22. Xu Y, Lin D, Li S, Li G, Shyamala SG, Barish PA, Vernon MM, Pan J, Ogle WO (2009) Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress. Neuropharmacology 57:463–471

    Article  PubMed  CAS  Google Scholar 

  23. Jaques JADS, Rezer JFP, Carvalho FB, da Rosa MM, Gutierres JM, Goncalves JF, Schmatz R, de Bairros AV, Mazzanti CM, Rubin MA, Schetinger MRC, Leal DBR (2012) Curcumin protects against cigarette smoke-induced cognitive impairment and increased acetylcholinesterase activity in rats. Physiol Behav 106:664–669

    Article  PubMed  CAS  Google Scholar 

  24. Dong S, Zeng Q, Mitchell ES, Xiu J, Duan Y, Li C, Tiwari JK, Hu Y, Cao X, Zhao Z (2012) Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PLoS One 7:e31211

    Article  PubMed  CAS  Google Scholar 

  25. Reeta KH, Mehla J, Gupta YK (2010) Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats. Eur J Pharmacol 644:106–112

    Article  PubMed  CAS  Google Scholar 

  26. Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Kazeminejad B (2010) Neuroprotective effects of the polyphenolic antioxidant agent, curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat. Pharmacol Biochem Behav 96:378–385

    Article  PubMed  CAS  Google Scholar 

  27. Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM (2001) Phenolic anti-inflammatory antioxidant reversal of abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 22:993–1005

    Article  PubMed  CAS  Google Scholar 

  28. Wu A, Ying Z, Gomez-Pinilla F (2006) Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition. Exp Neurol 197:309–317

    Article  PubMed  CAS  Google Scholar 

  29. Baum L, Ng A (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis 6:367–377 (discussion 443–369)

    PubMed  CAS  Google Scholar 

  30. Coultrap SJ, Bickford PC, Browning MD (2008) Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP. Age (Dordr) 30:263–272

    Article  Google Scholar 

  31. Long LH, Liu RL, Wang F, Liu J, Hu ZL, Xie N, Jin Y, Fu H, Chen JG (2009) Age-related synaptic changes in the CA1 stratum radiatum and spatial learning impairment in rats. Clin Exp Pharmacol Physiol 36:675–681

    Article  PubMed  CAS  Google Scholar 

  32. Zeng Y, Tan M, Kohyama J, Sneddon M, Watson JB, Sun YE, Xie CW (2011) Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging. J Neurosci 31:17800–17810

    Article  PubMed  CAS  Google Scholar 

  33. Ahmed T, Gilani AH, Hosseinmardi N, Semnanian S, Enam SA, Fathollahi Y (2011) Curcuminoids rescue long-term potentiation impaired by amyloid peptide in rat hippocampal slices. Synapse 65:572–582

    Article  PubMed  CAS  Google Scholar 

  34. Engert F, Bonhoeffer T (1997) Synapse specificity of long-term potentiation breaks down at short distances. Nature 388:279–284

    Article  PubMed  CAS  Google Scholar 

  35. Foster TC (2012) Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca(2)(+) channels in senescent synaptic plasticity. Prog Neurobiol 96:283–303

    Article  PubMed  CAS  Google Scholar 

  36. Foster TC (1999) Involvement of hippocampal synaptic plasticity in age-related memory decline. Brain Res Brain Res Rev 30:236–249

    Article  PubMed  CAS  Google Scholar 

  37. Foster TC, Norris CM (1997) Age-associated changes in Ca(2+)-dependent processes: relation to hippocampal synaptic plasticity. Hippocampus 7:602–612

    Article  PubMed  CAS  Google Scholar 

  38. Bach ME, Barad M, Son H, Zhuo M, Lu YF, Shih R, Mansuy I, Hawkins RD, Kandel ER (1999) Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci USA 96:5280–5285

    Article  PubMed  CAS  Google Scholar 

  39. Robillard JM, Gordon GR, Choi HB, Christie BR, MacVicar BA (2011) Glutathione restores the mechanism of synaptic plasticity in aged mice to that of the adult. PLoS One 6:e20676

    Article  PubMed  CAS  Google Scholar 

  40. Foster TC (2002) Regulation of synaptic plasticity in memory and memory decline with aging. Prog Brain Res 138:283–303

    Article  PubMed  CAS  Google Scholar 

  41. Foster TC (2007) Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell 6:319–325

    Article  PubMed  CAS  Google Scholar 

  42. Bodhinathan K, Kumar A, Foster TC (2010) Intracellular redox state alters NMDA receptor response during aging through Ca2+/calmodulin-dependent protein kinase II. J Neurosci 30:1914–1924

    Article  PubMed  CAS  Google Scholar 

  43. Khuwaja G, Khan MM, Ishrat T, Ahmad A, Raza SS, Ashafaq M, Javed H, Khan MB, Khan A, Vaibhav K, Safhi MM, Islam F (2011) Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical and immunohistochemical studies. Brain Res 1368:254–263

    Article  PubMed  CAS  Google Scholar 

  44. Cole GM, Teter B, Frautschy SA (2007) Neuroprotective effects of curcumin. Adv Exp Med Biol 595:197–212

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Key Medical Projects of Health Bureau of Hebei Province (20110160), China, and the Doctoral Science Research Fund of Hebei United University. We are grateful to Mr. Edward Diaz (Headmaster of Tangshan Astone English School) for language critical review of the manuscript.

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Authors and Affiliations

  1. Jitang College of Hebei United University, Tangshan, 063000, People’s Republic of China

    Yue-Fa Cheng, Lan Guo, Yue-Sheng Xie, Ying-Shuo Liu & Jun Zhang

  2. College of Nursing and Rehabilitation, Hebei United University, Tangshan, 063000, People’s Republic of China

    Qing-Wen Wu

  3. Affiliated Hospital of Hebei United University, Tangshan, 063000, People’s Republic of China

    Jian-Min Li

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  1. Yue-Fa Cheng
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  2. Lan Guo
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Correspondence to Yue-Fa Cheng.

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Cheng, YF., Guo, L., Xie, YS. et al. Curcumin Rescues Aging-Related Loss of Hippocampal Synapse Input Specificity of Long Term Potentiation in Mice. Neurochem Res 38, 98–107 (2013). https://doi.org/10.1007/s11064-012-0894-y

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  • DOI: https://doi.org/10.1007/s11064-012-0894-y

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