Comparison of the regional distribution of transferrin receptors and aluminium in the forebrain of chronic renal dialysis patients

Morris, Christopher M.; Candy, J.; Oakley, Arthur E.; Taylor, Geoffrey A.; Mountfort, Simon A.; Bishop, H.E.; Ward, M. K.; Bloxham, C. A.; Edwardson, James A.

doi:10.1016/0022-510x(89)90238-4

Cited by 62 publications

(37 citation statements)

References 26 publications

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“…Thus, the cerebral cortex which contains relatively little non-haem iron has neurones with high densities of transferrin receptors [12]. In contrast, the striatum has a high non-haem iron content and neurones with relatively low densities of transferrin receptors [12].…”

Section: Discussionmentioning

confidence: 99%

“…The more intense immunostaining found in large neurones in areas such as the amygdala and brainstem may reflect the high densities of transferrin receptors on such cells [3,12], Transferrinmediated iron uptake into these neurones appears to be related to their total respiratory rate, the iron being utilized in the production of iron-containing enzymes of the mito chondrial respiratory chain such as cytochrome oxidase [3 J.…”

Section: Discussionmentioning

confidence: 99%

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Immunocytochemical Localisation of Transferrin in the Human Brain

Morris¹,

Candy²,

Bloxham

et al. 1992

Cells Tissues Organs

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Immunocytochemical studies on the adult human brain have shown that transferrin is localized within three main compartments in the adult human brain. Oligodendrocytes and some astrocytes together with cells of the choroid plexus showed the highest intensity of staining. Neuronal staining occurred mainly within pyramidal or large polygonal cells, but this showed considerable regional variation being most marked in areas such as the cerebral cortex, amygdala, hippocampus, brainstem and cerebellar Purkinje cells. Small neurones such as caudate interneurones and granule cells showed relatively low activity. Diffuse immunostaining of the neuropil was evident, particularly where heavy neuronal or glial staining occurred. Immunostaining was also observed in white-matter fibre tracts. This pattern of distribution helps to provide a model for the mechanisms responsible for iron homeostasis in the normal brain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunocytochemical Localisation of Transferrin in the Human Brain

Morris¹,

Candy²,

Bloxham

et al. 1992

Cells Tissues Organs

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“…For example, the iron-rich areas of the substantia nigra and globus pallidus receive input from the nucleus accumbens and caudate putamen, areas rich in transferrin receptors (178). Transferrin and its receptor may also transport other cations such as aluminum (179). This mode of access of neurotoxic metals into the CNS may also explain earlier observations of enhanced lead absorption during iron deficiency and anemia (180).…”

Section: Practical Considerations In the Experimental Design Of Pharmmentioning

confidence: 86%

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

DORMAN

Allen

Byczkowski

et al. 2001

Environ Health Perspect

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We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.

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“…Aluminium (Al) is a significant but con-troversial environmental risk factor for AD [6,7]. Evidence of Al involvement comes from several sources: the presence of alumino-silicate cores in senile plaques [8] and accumulation of Al in brain areas vulnerable in AD [9,10], the detection of immature senile plaques and Alzheimer-like changes in tau protein in postmortem brain from renal dialysis patients (with no symptoms of dialysis encephalopathy) [11,12] and the increased prevalence of AD in areas with high levels of Al in drinking water [13,14].…”

Section: Introductionmentioning

confidence: 99%

Absorption of Aluminium-26 in Alzheimer’s Disease, Measured Using Accelerator Mass Spectrometry

Moore

Day

Taylor

et al. 2000

Dement Geriatr Cogn Disord

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Although chromosomal abnormalities underpin some early onset cases of familial Alzheimer’s disease (AD), most cases are sporadic and not associated with such abnormalities. Aluminium (Al) is a significant but controversial risk factor for sporadic AD, and studies have reported associations between Al and the principal pathological features of AD, senile plaques and neurofibrillary tangles. The present study measured gastrointestinal (GI) absorption of Al under normal dietary conditions using ²⁶Al tracer and accelerator mass spectrometry (AMS). Following overnight fast, 13 AD patients (aged 63–76 years) and 13 age-matched controls (aged 62–76 years) ingested a fruit drink containing 27 ng ²⁶Al. Plasma samples were obtained before and 1 h after the drink and from these the fraction of ²⁶Al absorbed across the GI tract was estimated. The GI tract rigorously excludes Al with only 0.06–0.1% of the ingested Al being absorbed. The mean fraction absorbed by AD subjects exceeded controls by a factor of 1.64 (p≤0.05, Anova). AMS is capable of determining <10^–16 g of ²⁶Al with many orders of magnitude more sensitivity than other techniques. Using this sensitivity, we have shown, under normal physiological conditions, that the ability of the GI tract to exclude Al is reduced in AD, possibly leading to greater systemic exposure to Al. Public health measures to limit Al dietary uptake or bioavailability may decrease the prevalence of AD in the community and should be considered.

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Comparison of the regional distribution of transferrin receptors and aluminium in the forebrain of chronic renal dialysis patients

Cited by 62 publications

References 26 publications

Immunocytochemical Localisation of Transferrin in the Human Brain

Immunocytochemical Localisation of Transferrin in the Human Brain

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

Absorption of Aluminium-26 in Alzheimer’s Disease, Measured Using Accelerator Mass Spectrometry

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