title: Brain iron deficiency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus.
abstract: While iron deficiency is not perceived as a life threatening disorder, it is the most prevalent nutritional abnormality in the world, and a better understanding of modes and sites of action, can help devise better treatment programs for those who suffer from it. Nowhere is this more important than in infants and children that make up the bulk of iron deficiency in society. Although the effects of iron deficiency have been extensively studied in systemic organs, until very recently little attention was paid to its effects on brain function. The studies of Oski at Johns Hopkin Medical School in 1974, demonstrating the impairment of learning in young school children with iron deficiency, prompted us to study its relevance to brain biochemistry and function in an animal model of iron deficiency. Indeed, rats made iron deficient have lowered brain iron and impaired behaviours including learning. This can become irreversible especially in newborns, even after long-term iron supplementation. We have shown that in this condition it is the brain striatal dopaminergic-opiate system which becomes defective, resulting in alterations in circadian behaviours, cognitive impairment and neurochemical changes closely associated with them. More recently we have extended these studies and have established that cognitive impairment may be closely associated with neuroanatomical damage and zinc metabolism in the hippocampus due to iron deficiency, and which may result from abnormal cholinergic function. The hippocampus is the focus of many studies today, since this brain structure has high zinc concentration and is highly involved in many forms of cognitive deficits as a consequence of cholinergic deficiency and has achieved prominence because of dementia in ageing and Alzheimer's disease. Thus, it is now apparent that cognitive impairment may not be attributed to a single neurotransmitter, but rather, alterations and interactions of several systems in different brain regions. In animal models of iron deficiency it is apparent that dopaminergic interaction with the opiate system and cholinergic neurotransmission may be defective.
authors.affiliation: Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, Haifa, Israel. youdim@tx.technion.ac.il
authors.forename: M B H
authors.initials: MB
authors.lastname: Youdim
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D019189:Iron Metabolism Disorders / Q000145:classification / Q000150:complications*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology
references.citation: Am J Med Sci. 1999 Oct;318(4):230-40
references.pmid: 10522551
references.citation: J Comp Neurol. 1998 Aug 31;398(3):420-30
references.pmid: 9714152
references.citation: Physiol Behav. 1984 Mar;32(3):469-74
references.pmid: 6589654
references.citation: J Immunol. 2001 Jun 15;166(12):7527-33
references.pmid: 11390507
references.citation: Neurosci Res. 1993 Aug;17(3):187-203
references.pmid: 8233123
references.citation: J Nutr. 1996 Mar;126(3):693-701
references.pmid: 8598555
references.citation: J Nutr. 1977 Jun;107(6):1075-81
references.pmid: 864518
references.citation: Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):517-28
references.pmid: 10872739
references.citation: Life Sci. 1986 Mar 24;38(12):1081-8
references.pmid: 2870405
references.citation: Life Sci. 1991;48(12):PL57-62
references.pmid: 1848338
references.citation: J Neurochem. 1989 Feb;52(2):515-20
references.pmid: 2911028
references.citation: Neurosci Lett. 1995 Apr 28;190(1):21-4
references.pmid: 7624046
references.citation: J Neurochem. 1988 May;50(5):1434-7
references.pmid: 2966235
references.citation: Acta Paediatr Scand Suppl. 1989;361:71-7
references.pmid: 2485588
references.citation: Nature. 1993 Jan 7;361(6407):31-9
references.pmid: 8421494
references.citation: Eur J Pharmacol. 1999 Dec 3;385(2-3):231-7
references.pmid: 10607881
references.citation: Biol Trace Elem Res. 1991 Jun;29(3):257-65
references.pmid: 1726408
references.citation: Pediatrics. 1989 Jul;84(1):7-17
references.pmid: 2472596
references.citation: Neuroscience. 1988 May;25(2):525-32
references.pmid: 3041310
references.citation: Brain Res. 1983 Aug 29;273(2):335-9
references.pmid: 6616240
references.citation: J Nutr. 1998 Dec;128(12):2295-8
references.pmid: 9868172
references.citation: Biol Trace Elem Res. 1989 Nov;22(2):141-52
references.pmid: 2484235
references.citation: Psychosom Med. 1964 Mar-Apr;26:125-34
references.pmid: 14132974
references.citation: J Nutr. 1999 Jan;129(1):199-206
references.pmid: 9915900
references.citation: Ann Nutr Metab. 1990;34(5):280-7
references.pmid: 2244749
references.citation: J Neurol Sci. 1995 Dec;134 Suppl:45-51
references.pmid: 8847544
references.citation: Brain Res. 1990 Jun 4;518(1-2):31-9
references.pmid: 2390723
references.citation: Brain Res. 1981 May 11;212(1):230-3
references.pmid: 7013906
references.citation: Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):501-15
references.pmid: 10872738
references.citation: J Pediatr. 1996 Sep;129(3):382-9
references.pmid: 8804327
references.citation: J Neurochem. 1991 Nov;57(5):1584-92
references.pmid: 1919575
references.citation: Br J Haematol. 1975 Oct;31(2):209-15
references.pmid: 1201239
references.citation: Brain Res. 1996 Sep 2;732(1-2):113-20
references.pmid: 8891275
references.citation: Neurochem Res. 1996 Aug;21(8):915-22
references.pmid: 8895845
references.citation: Proc Natl Acad Sci U S A. 1983 Jun;80(12):3841-4
references.pmid: 6190182
references.citation: Pflugers Arch. 1994 Jul;427(5-6):481-6
references.pmid: 7971146
references.citation: Trends Neurosci. 1995 Aug;18(8):350-5
references.pmid: 7482797
references.citation: Ciba Found Symp. 1976 Dec 7-9;(51):201-25
references.pmid: 1052031
references.citation: Pharmacol Biochem Behav. 1986 Jul;25(1):141-4
references.pmid: 3018790
references.citation: Pediatr Pathol Lab Med. 1996 May-Jun;16(3):509-19
references.pmid: 9025849
references.citation: J Comp Neurol. 1995 Apr 24;355(1):111-23
references.pmid: 7636007
references.citation: Nat Rev Neurosci. 2004 Nov;5(11):863-73
references.pmid: 15496864
references.citation: J Neurochem. 1986 Sep;47(3):794-9
references.pmid: 2942640
references.citation: Prog Hematol. 1986;14:23-53
references.pmid: 3511517
references.citation: Hokkaido Igaku Zasshi. 1998 May;73(3):215-25
references.pmid: 9719948
references.citation: J Neural Transm (Vienna). 2002 Oct;109(10):1241-56
references.pmid: 12373558
references.citation: J Neurochem. 1992 Mar;58(3):1104-9
references.pmid: 1346626
references.citation: J Nutr. 1997 Oct;127(10):2030-8
references.pmid: 9311961
references.citation: J Anat. 1995 Feb;186 ( Pt 1):165-73
references.pmid: 7649811
references.citation: Brain Res Mol Brain Res. 1999 Mar 5;65(2):186-97
references.pmid: 10064889
references.citation: Am J Clin Nutr. 1989 Sep;50(3 Suppl):618-25; discussion 625-9
references.pmid: 2570524
references.citation: J Neurochem. 1958 Oct;3(1):41-51
references.pmid: 13611557
references.citation: Adv Pediatr. 1988;35:331-59
references.pmid: 3055862
references.citation: Nature. 1984 Apr 19-25;308(5961):736-8
references.pmid: 6717567
references.citation: J Pediatr. 1973 May;82(5):827-30
references.pmid: 4698956
references.citation: Am J Clin Nutr. 1989 Sep;50(3 Suppl):565-705
references.pmid: 2773837
references.citation: Am J Clin Nutr. 1989 Sep;50(3 Suppl):607-15; discussion 615-7
references.pmid: 2773840
references.citation: Acta Neuropathol. 1989;79(2):129-36
references.pmid: 2596262
references.citation: Int J Dev Neurosci. 1986;4(1):81-8
references.pmid: 2844061
references.citation: J Neurochem. 1987 Nov;49(5):1523-9
references.pmid: 3312497
references.citation: Neuroscience. 1988 Oct;27(1):333-45
references.pmid: 3200444
references.citation: Eur J Pharmacol. 1984 Sep 17;104(3-4):245-51
references.pmid: 6094214
references.citation: Glia. 1996 Jun;17(2):83-93
references.pmid: 8776576
references.citation: Prev Med. 1998 Mar-Apr;27(2):189-94
references.pmid: 9578993
references.citation: Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):743-60
references.pmid: 10875437
references.citation: N Engl J Med. 1991 Sep 5;325(10):687-94
references.pmid: 1870641
references.citation: J Nutr. 2000 Feb;130(2):254-63
references.pmid: 10720179
references.citation: Biol Trace Elem Res. 1996 Oct-Nov;55(1-2):39-54
references.pmid: 8971353
references.citation: J Neurosci Res. 1994 Mar 1;37(4):461-5
references.pmid: 8021970
references.citation: Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):491-500
references.pmid: 10872737