Blood withdrawal affects iron store dynamics in primates with consequences on monoaminergic system function.

C. Hyacinthe, P. De Deurwaerdere, T. Thiollier, Q. Li, E. Bezard, I. Ghorayeb
Neuroscience. 2015-04-01; 290: 621-635
DOI: 10.1016/j.neuroscience.2015.01.057

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1. Neuroscience. 2015 Apr 2;290:621-35. doi: 10.1016/j.neuroscience.2015.01.057.
Epub 2015 Feb 4.

Blood withdrawal affects iron store dynamics in primates with consequences on
monoaminergic system function.

Hyacinthe C(1), De Deurwaerdere P(2), Thiollier T(3), Li Q(4), Bezard E(5),
Ghorayeb I(6).

Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France. Electronic address:
.
(2)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France. Electronic address: .
(3)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France; Cynbiose, F-69280 Marcy l’Etoile, France.
Electronic address: .
(4)Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing,
China; Motac Neuroscience, Manchester, United Kingdom. Electronic address:
.
(5)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France; Institute of Lab Animal Sciences, China Academy
of Medical Sciences, Beijing, China; Motac Neuroscience, Manchester, United
Kingdom. Electronic address: .
(6)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France; Département de Neurophysiologie Clinique, CHU de
Bordeaux Pellegrin, F-33000 Bordeaux, France. Electronic address:
.

Iron homeostasis is essential for the integrity of brain monoaminergic functions
and its deregulation might be involved in neurological movement disorders such as
the restless legs syndrome (RLS). Although iron metabolism breakdown
concomitantly appears with monoaminergic system dysfunction in iron-deficient
rodents and in RLS patients, the direct consequences of peripheral iron
deficiency in the central nervous system (CNS) of non-human primates have
received little attention. Here, we evaluated the peripheral iron-depletion
impact on brain monoamine levels in macaque monkeys. After documenting circadian
variations of iron and iron-related proteins (hemoglobin, ferritin and
transferrin) in both serum and cerebrospinal fluid (CSF) of normal macaques,
repeated blood withdrawals (RBW) were used to reduce peripheral iron-related
parameter levels. Decreased serum iron levels were paradoxically associated with
increased CSF iron concentrations. Despite limited consequences on tissue
monoamine contents (dopamine – DA, 3, 4-dihydroxyphenylacetic acid – DOPAC,
homovanillic acid, L-3, 4-dihydroxyphenylalanine – L-DOPA, 5-8 hydroxytryptamine
– 5-HT, 5-hydroxyindoleacetic acid – 5-HIAA and noradrenaline) measured with
post-mortem chromatography, we found distinct and region-dependent relationships
of these tissue concentrations with CSF iron and/or serum iron and/or blood
hemoglobin. Additionally, striatal extracellular DA, DOPAC and 5-HIAA levels
evaluated by in vivo microdialysis showed a substantial increase, suggesting an
overall increase in both DA and 5-HT tones. Finally, a trending increase in
general locomotor activity, measured by actimetry, was observed in the most serum
iron-depleted macaques. Taken together, our data are compatible with an increase
in nigrostriatal DAergic function in the event of iron deficiency and point to a
specific alteration of the 5-HT/DA interaction in the CNS that is possibly
involved in the etiology of RLS.

Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuroscience.2015.01.057
PMID: 25662508 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus