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Functional Consequences of Iron Overload in Catecholaminergic Interactions: the Youdim Factor

Neurochemical Research volume 32, pages 1625–1639 (2007)Cite this article

Abstract

The influence of postnatal iron overload upon implications of the functional and interactive role of dopaminergic and noradrenergic pathways that contribute to the expressions of movement disorder and psychotic behaviours in mice was studied in a series of experiments. (1) Postnatal iron overload at doses of 7.5 mg/kg (administered on Days 10–12 post partum) and above, invariably induced a behavioural syndrome consisting of an initial (1st 20–40 min of a 60-min test session) hypoactivity followed by a later (final 20 min of a 60-min test session) hyperactivity, when the mice were tested at adult ages (age 60 days or more). (2) Following postnatal iron overload, subchronic treatment with the neuroleptic compounds, clozapine and haloperidol, dose-dependently reversed the initial hypoactivity and later hyperactivity induced by the metal. Furthermore, DA D2 receptor supersensitivity (as assessed using the apomorphine-induced behaviour test) was directly and positively correlated with iron concentrations in the basal ganglia. (3) Brain noradrenaline (NA) denervation, using the selective NA neurotoxin, DSP4, prior to administration of the selective DA neurotoxin, MPTP, exacerbated both the functional (hypokinesia) and neurochemical (DA depletion) effects of the latter neurotoxin. Treatment with L-Dopa restored motor activity only in the animals that had not undergone NA denervation. These findings suggest an essential neonatal iron overload, termed “the Youdim factor”, directing a DA–NA interactive component in co-morbid disorders of nigrostriatal-limbic brain regions.

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  1. Department of Neuroscience & Psychiatry, Ulleråker, University of Uppsala, Uppsala, 750 17, Sweden

    Trevor Archer

  2. Department of Health and Behavioural Science, Kalmar University, Kalmar, 391, Sweden

    Trevor Archer

  3. Department of Psychology, University of Göteborg, Box 500, Goteborg, 450 30, Sweden

    Trevor Archer & Anders Fredriksson

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Correspondence to Trevor Archer.

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Special issue dedicated to Dr. Moussa Youdim.

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Archer, T., Fredriksson, A. Functional Consequences of Iron Overload in Catecholaminergic Interactions: the Youdim Factor. Neurochem Res 32, 1625–1639 (2007). https://doi.org/10.1007/s11064-007-9358-1

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Keywords

  • Iron administration
  • Postnatal
  • Fe2+
  • Vehicle
  • Clozapine
  • Haloperidol
  • Basal ganglia
  • Motor deficits
  • Locomotion
  • Rearing
  • Total activity
  • DA D2 receptor supersensitivity
  • Behavioural deficits