Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability

Zucca, Fabio A.; Bellei, Chiara; Giannelli, Serena; Terreni, M. R.; Gallorini, M.; Rizzio, E.; Pezzoli, Gianni; Albertini, Alberto; Zecca, Luigi

doi:10.1007/s00702-006-0453-2

Cited by 106 publications

(132 citation statements)

References 45 publications

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“…8 In this study, the contrast ratios of the LC tended to be relatively low in young and elderly subjects and relatively high in middle-aged subjects. This agerelated tendency was statistically signiˆcant and can beˆtted to an upwardly convex quadratic curve.…”

Section: Discussionmentioning

confidence: 93%

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Age-related Changes in Locus Ceruleus on Neuromelanin Magnetic Resonance Imaging at 3 Tesla

et al. 2006

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Purpose: To investigate age-related changes in the locus ceruleus (LC) in healthy subjects using neuromelanin magnetic resonance (MR) imaging at 3 Tesla.Methods: We examined 64 healthy volunteers (aged 23 to 80 years) using neuromelaninsensitive T 1 -weighted images and measured the contrast of areas of high signal intensity corresponding to the LC.Results: A pair of punctate areas of high signal intensity that represented neuromelanin within the noradrenergic neurons of the LC was easily recognized in all subjects. The contrast ratio of the LC to the adjacent pontine tegmentum increased to the age of 40 to 59 years and gradually and signiˆcantly decreased in elderly subjects. This correlates well with pathologically proven age-related changes in neuromelanin content within the LC.Conclusion: Age-related variance should be considered when determining the existence of abnormalities in the LC.

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Section: Discussionmentioning

confidence: 93%

“…In this study, we quantitatively examined the signal intensity of the LC in young to elderly adults to elucidate whether the neuromelanin-generated contrast depends on age-related changes in neuromelanin concentration, which has been pathologically proven. [6][7][8] …”

Section: Introductionmentioning

confidence: 99%

Age-related Changes in Locus Ceruleus on Neuromelanin Magnetic Resonance Imaging at 3 Tesla

et al. 2006

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“…Some factors potentially modulate the signal intensity of the SNc and LC on neuromelanin-sensitive MRI. The neuronal number and intraneuronal neuromelanin content of the SNc and LC change substantially with age [27,28]. Our preliminary study showed a significant age-dependent variance in the signal intensity of the LC [3]; this variance should be considered while evaluating signal alteration.…”

Section: What Are the Limitations And Future Prospects Of Neuromelanimentioning

confidence: 99%

Neuromelanin-Sensitive MRI

et al. 2008

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The basics and the technique of magnetic resonance imaging (MRI) for visualizing the neuromelanin present in dopaminergic and noradrenergic nuclei in the substantia nigra pars compacta (SNc) and locus caeruleus (LC) are introduced. Neuromelanin, a black pigment produced during catecholamine synthesis, has paramagnetic T1-shortening effects. Conventional MRI techniques fail to depict the contrast generated by neuromelanin, but neuromelanin-sensitive T1-weighted fast spin echo technique at 3 T allows the direct visualization of the SNc and LC as hyperintense areas. In Parkinson's disease, neuromelanin-related signals from the SNc and LC are diminished, suggesting neuronal degeneration in both the nuclei. In depression and schizophrenia, signals from the LC are reduced while those from the SNc are augmented, suggesting monoamine and dopamine hypotheses, respectively. Neuromelanin-sensitive MRI is a promising technique to elucidate the pathologic or functional changes in the catecholamine neurons of the brain stem that occur in degenerative and psychiatric diseases. ZusammenfassungDie Grundlagen und die Technik der Kernspintomographie (MRT) zur Visualisierung des in den dopaminergen und noradrenergen Nuklei in der Pars compacta der Substantia nigra (SNc) und im Locus caeruleus (LC) vorhandenen Neuromelanins werden vorgestellt. Neuromelanin, ein schwarzes Pigment, welches durch die Katecholaminsynthese entsteht, hat eine paramagnetische, T1-verkürzende Wirkung. Konventionelle MRT-Techniken sind nicht in der Lage, den durch das Neuromelanin generierten Kontrast darzustellen. Eine neuromelaninsensitive, T1-gewichtete, schnelle Spinechotechnik bei 3 T hingegen erlaubt eine unmittelbare Visualisierung der SNc und des LC als hyperintense Areale. Bei der Parkinson-Krankheit sind die neuromelaninbedingten Signale aus der SNc und dem LC vermindert und lassen auf eine neuronale Degeneration in beiden Nuklei schließen. Bei Depressionen und Schizophrenie sind die Signale aus dem LC vermindert, während die Signale aus der SNc erhöht sind und auf eine monoamine bzw. dopamine Hypothese hindeuten. Die neuromelaninsensitive MRT ist eine vielversprechende Technik zur Klärung der bei degenerativen und psychiatrischen Krankheiten vorkommenden pathologischen oder funktionellen Veränderungen der katecholaminen Neuronen des Hirnstamms. IntroductionIt is widely known that some catecholamine neurons in the human brain stem, such as those of the substantia nigra pars compacta (SNc) and locus caeruleus (LC), contain a black pigment called neuromelanin [1]. These neuromelanin-containing nuclei can be easily identified as black areas in gross specimens. However, these nuclei have remained invisible on magnetic resonance imaging (MRI), and the neuromelanin-generated contrast has hardly been studied. Recently, we proposed a new MRI technique that can depict the neuromelanin-related contrast generated by these nuclei and demonstrate pathologic changes occurring in some degenerative and psychiatric diseases [2][3][4][5]. In this review, we introduce...

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“…Neurons inconsistently stain for transferrin, whereas neuronal iron is present predominantly in the form of neuromelanin. 59,72 In microglia and astrocytes, an increase in iron staining correlates positively with the age of the subject. Conversely, oligodendrocytes do not show an increase in staining iron with age.…”

Section: Endogenous Protection From Iron-related Damagementioning

confidence: 99%

“…73 With increasing age, iron increases in astrocytes and microglia, although the primary cellular repository for iron (i.e., the oligodendrocyte) undergoes little accumulation. 72,74 Bartzokis 79,80 has demonstrated by MRI that women have significantly lower ferritin iron in areas such as the caudate, thalamus, and white matter than men. The group speculates that the slower increase of iron in the female brain may to a certain extent explain why women tend to develop AD and PD at a more advanced age then men.…”

Section: Endogenous Protection From Iron-related Damagementioning

confidence: 99%

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

et al. 2007

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Summary:Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathological processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article, we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development.

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Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability

Cited by 106 publications

References 45 publications

Age-related Changes in Locus Ceruleus on Neuromelanin Magnetic Resonance Imaging at 3 Tesla

Age-related Changes in Locus Ceruleus on Neuromelanin Magnetic Resonance Imaging at 3 Tesla

Neuromelanin-Sensitive MRI

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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