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Iron-dextran injection into the substantia nigra in rats decreases striatal dopamine content ipsilateral to the injury site and impairs motor function

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Abstract

Iron chloride injections into the rat SNc can cause chronic decreases in striatal dopamine (DA) levels. However, changes in striatal DA content after iron-dextran injection into rat SNc have not been completely elucidated. The aim of this work was to measure striatal DA concentrations after iron-dextran injection into the SNc. We divided 40 male Wistar rats into five groups, including control, saline injected then sacrificed 7 days or 30 days later, and iron-dextran injected then sacrificed 7 days or 30 days later. Striatal DA content was measured in control animals and in all animals sacrificed 7 days or 30 days after injection, and motor performance was assessed in iron-dextran and saline injected groups 30 days after injection. The striatal DA levels were determined using HPLC. There were significant (P < 0.05) decreases in DA concentrations in the striatum ipsilateral to the injection site in the iron-dextran treated rats compared to control and saline-injected rats. There were no significant differences in DA concentration between the sham-operated (i.e., saline-injected) and control rats. We also observed motor deficits in the iron-dextran injected rats. The striatal DA reduction observed after iron-dextran injection may be attributable to iron-induced oxidative injury in the SNc. Motor deficits, in turn, may be explained by subsequent disturbances in striatal and cortical dopaminergic neuromodulation.

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References

  • Arias-Montaño J-A, Florán B, García M, Aceves J, Young JM (2001) Histamine H3 receptor-mediated inhibition of depolarization-induced, dopamine D1 receptor-dependent release of [3H]-γ-aminobutyric acid from rat striatal slices. Br J Pharmacol 133:165–171

    Article  PubMed  Google Scholar 

  • Ben-Shachar D, Youdim MB (1991) Intranigral iron injection induced behavioral and biochemical “parkinsonism” in rats. J Neurochem 57:2133–5

    Article  CAS  PubMed  Google Scholar 

  • Bolam JP, Hanley JJ, Booth PAC, Bevan MD (2000) Synaptic organisation of the basal ganglia. J Anat 196:527–542

    Article  CAS  PubMed  Google Scholar 

  • Braughler JM (1985) Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids. J Neurochem 44:1282–1288

    Article  CAS  PubMed  Google Scholar 

  • Bueno-Nava A, Montes S, DelaGarza-Montano P, Alfaro-Rodriguez A, Ortiz A, Gonzalez-Pina R (2008) Reversal of noradrenergic depletion and lipid peroxidation in the pons after brain injury correlates with motor function recovery in rats. Neurosci Lett 443:32–36

    Article  CAS  PubMed  Google Scholar 

  • Cantuti-Castelvetri I, Shukitt-Hale B, Joseph JA (2003) Dopamine neurotoxicity: age-dependent behavioral and histological effects. Neurobiol Aging 24:697–706

    Article  CAS  PubMed  Google Scholar 

  • Chan PH, Kerlan R, Fishman RA (1983) Reductions of gamma-aminobutyric acid and glutamate uptake and (Na+ + K+)-ATPase activity in brain slices and synaptosomes by arachidonic acid. J Neurochem 40:309–316

    Article  CAS  PubMed  Google Scholar 

  • Cochrane CJ, Schraufstatter IV, Hyslop P, Jackson J (1988) Cellular and biochemical events in oxidants injury. In: Halliwell B (ed) Oxygen radicals and tissue injury. FASEB 49–54

  • Cox JSG, Moss GF, Bremner I, Reason J (1968) Intravenous iron-dextran: studies on unsaturated iron-binding capacity. J Clin Path 21:611–615

    Article  CAS  PubMed  Google Scholar 

  • Davies KJ (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp 61:1–31

    CAS  PubMed  Google Scholar 

  • Garcia JH, Wagner S, Liu KF, Hu XJ (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 26:627–35

    CAS  PubMed  Google Scholar 

  • Gasche C, Lomer MCE, Cavill I, Weiss G (2004) Iron, anaemia, and inflammatory bowel diseases. Gut 53:1190–1197

    Article  CAS  PubMed  Google Scholar 

  • González-Piña R, Paz C (1997) Brain monoamine changes in rats after short periods of ozone exposure. Neurochem Res 22:63–6

    Article  PubMed  Google Scholar 

  • Gonzalez-Pina R, Bueno-Nava A, Montes S, Alfaro-Rodríguez A, González-Maciel A, Reynoso-Robles R, Ayala-Guerrero F (2006) Pontine and cerebellar norepinephrine content in adult rats recovering from focal cortical injury. Neurochem Res 31:1443–9

    Article  CAS  PubMed  Google Scholar 

  • Gregory A, Hayflick SJ (2005) Neurodegeneration with brain iron accumulation. Folia Neuropathol 43:286–296

    CAS  PubMed  Google Scholar 

  • Groenewegen HJ (2003) The basal ganglia and motor control. Neural Plast 10:107–120

    Article  PubMed  Google Scholar 

  • Halliwell B (1987) Oxidants and human disease: some new concepts. FASEB J 1:358–354

    CAS  PubMed  Google Scholar 

  • Huff RM (1996) Signal transduction pathways modulated by the D2 subfamily of dopamine receptors. Cell Signal 8:453–459

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Song N, Wang J, Ren L-Y, Xie JX (2007) Peripheral iron dextran induced degeneration of dopaminergic neurons in rat substantia nigra. Neurochem Int 51:32–36

    Article  CAS  PubMed  Google Scholar 

  • Kandel ER, Schwartz JH, Jessel TM (2000) Principles of neural science. McGraw-Hill, New York

    Google Scholar 

  • Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Invest 111:785–793

    CAS  PubMed  Google Scholar 

  • Kristensson K, Bornstein BM (1974) Effects of iron-containing substances of nervous tissue in vitro. Acta Neuropathol (Berl) 28:281–292

    Article  CAS  Google Scholar 

  • Lin AM (2001) Coexistence of zinc and iron augmented oxidative injuries in the nigrostriatral dopaminergic system of SD rats. Free Radic Biol Med 30:225–231

    Article  CAS  PubMed  Google Scholar 

  • Lin AM, Yang CH, Chai CY (1998) Striatal dopamine dynamics are altered following an intranigral infusion of iron in adults rats. Free Radic Biol Med 24:988–93

    Article  CAS  PubMed  Google Scholar 

  • McConkey DJ, Hartzell P, Nicotera P, Wyllie AH, Orrenius S (1988) Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress. Toxicol Lett 42:123–30

    Article  CAS  PubMed  Google Scholar 

  • Meredith GE, Sonsalla P, Chesselet M-F (2008) Animal models of Parkinson’s disease progression. Acta Neuropathol 115:385–398

    Article  PubMed  Google Scholar 

  • Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, Laurie C, Gendelman HE (2006) Neuroinflammation, oxidative stress and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 6:261–281

    Article  CAS  PubMed  Google Scholar 

  • Muir AR, Golberg L (1961) Observations on subcutaneous macrophages. Phagocytosis of iron-dextran and ferritin synthesis. Q J Exp Physiol 46:289

    CAS  Google Scholar 

  • Olfert ED, Cross BM, McWilliam AA (eds) (1993) Guide to the care and use of experimental animals. Canadian Council on Animal Care

  • Pantoni L, Bartolini L, Pracucci G, Inzitari D (1998) Interrater agreement on a simple neurological score in rats. Stroke 29:871–872

    CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  • Qian MZ, Wang Q (1998) Expression of iron transport proteins and excessive iron accumulation in the brain in neurodegenerative disorders. Brain Res Rev 27:257–267

    Article  CAS  PubMed  Google Scholar 

  • Sengstock GJ, Olanow CW, Dunn AJ, Arendash GW (1992) Iron induces degeneration of nigrostriatal neurons. Brain Res Bull 28:645–649

    Article  CAS  PubMed  Google Scholar 

  • Sengstock GJ, Olanow CW, Dunn AJ, Barone S Jr, Arendash GW (1994) Progressive changes in striatal dopaminergic markers, nigral volume, and rotational behavior following iron infusion into the rat substantia nigra. Exp Neurol 130:82–94

    Article  CAS  PubMed  Google Scholar 

  • Subbarao KV, Richardson JS (1990) Iron-dependent peroxidation of rat brain: a regional study. J Neurosci Res 26:224–232

    Article  CAS  PubMed  Google Scholar 

  • Surmeier DJ, Ding J, Day M, Wang Z, Shen W (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 30:228–235

    Article  CAS  PubMed  Google Scholar 

  • Thompson KJ, Shoham S, Connor JR (2001) Iron and neurodegenerative disorders. Brain Res Bull 55:155–164

    Article  CAS  PubMed  Google Scholar 

  • Yoshida K, Kaneto K, Miyajima H, Tokuda T, Nakamura A, Kato M, Ikeda S-I (2000) Increased lipid peroxidation in the brains of aceruloplasmonemia patients. J Neurol Sci 175:91–95

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Alfonso Alfaro-Rodriguez.

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Bueno-Nava, A., Gonzalez-Pina, R. & Alfaro-Rodriguez, A. Iron-dextran injection into the substantia nigra in rats decreases striatal dopamine content ipsilateral to the injury site and impairs motor function. Metab Brain Dis 25, 235–239 (2010). https://doi.org/10.1007/s11011-010-9200-3

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