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Iodine Research

Resource Network of The Iodine Movement


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Brain (CNS)

Iodine deficiency was first linked with cretinism, a disease with many manifestations
including profound mental retardation.  Thus, iodine is profoundly linked to the brain,
especially through thyroid hormones (which include iodine).

Below are the primary researchers on iodine and the nervous system (and/or brain).
There are other important researcher included in the following pages but too many to list
in the introduction to this section.

Hetzel
has been instrumental in understanding cretinism, the effects of iodine on
neuropsychological development, and the various Iodine Deficiency Disorders (IDDs).

Andrasi has determined the iodine concentration in different parts of the human brain.

Cao and Hetzel discuss iodine and neuropsychological development, especially in cretinism.

Bernal has looked at iodine and brain development.

Cunnane discusses the importance of iodine in the evolution of the human brain.

Escobar and Mastorakos have focused on the role of thyroid hormone during early brain
development.

Gabrichidze shows that iodine affects the local blood flow in the hippocampus and cerebral cortex.

Ahmed,  Becker,  Bito,  Cserr,  Cutler, and Woodbury provide some early research on the levels
of iodine in the brain and cerebral spinal fluid, as well as possible iodine transport mechanisms.

Visser discusses how the deiodinases function in the brain.

Mitchell et al have researched the interactions of iodine and selenium deficiencies on the brain.

Rao discusses the role of goitrogens in brain development.

Adams found that iodine levels in hair were 45% lower in the children with autism.

Articles on myelin sheath development are found under Multiple Sclerosis


Adams
Sulfhydryl-reactive metals in autism.
Kern JK, Grannemann BD, Trivedi MH, Adams JB.
J Toxicol Environ Health A. 2007 Apr 15;70(8):715-21.
[abstract only]

This study examined the difference between sulfhydryl-reactive metals (mercury, lead, arsenic, and
cadmium) in the hair of 45 children with autism (1-6 yr of age) as compared to 45 gender-, age-, and
race-matched typical children. Hair samples were measured with inductively coupled mass
spectrometry. Some studies, such as Holmes et al. (2003), suggested that children with autism may
be poor detoxifiers relative to normally developing children. Metals that are not eliminated sequester
in the brain. Our study found that arsenic, cadmium, and lead were significantly lower in the hair of
children with autism than in matched controls. Mercury was in the same direction (lower in autism)
following the same pattern, but did not achieve statistical significance. The evidence from our study
supports the notion that children with autism may have trouble excreting these metals, resulting in a
higher body burden that may contribute to symptoms of autism.


Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and
associated conditions, and their mothers.
Adams JB, Holloway CE, George F, Quig D.
Biol Trace Elem Res. 2006 Jun;110(3):193-209.
[abstract only]

The objective of this study was to assess the levels of 39 toxic metals and essential minerals in hair
samples of children with autism spectrum disorders and their mothers compared to controls.
Inductively coupled plasma-mass spectrometry was used to analyze the elemental content of the hair
of children with autism spectrum disorders (n=51), a subset of their mothers (n=29), neurotypical
children (n=40), and a subset of their mothers (n=25). All participants were recruited from Arizona.
Iodine levels were 45% lower in the children with autism (p=0.005). Autistic children with pica had a
38% lower level of chromium (p=0.002). Autistic children with low muscle tone had very low levels of
potassium (-66%, p=0.01) and high zinc (31%, p=0.01). The mothers of young children with autism
had especially low levels of lithium (56% lower, p=0.005), and the young children (ages 3-6 yr) with
autism also had low lithium (-30%, p=0.04). Low iodine levels are consistent with previous reports of
abnormal thyroid function, which likely affected development of speech and cognitive skills. Low
lithium in the mothers likely caused low levels of lithium in the young children, which could have
affected their neurological and immunological development. Further investigations of iodine, lithium,
and other elements are warranted.


Ahmed
The iodide space in rabbit brain.
Ahmed N, Van Harreveld A.
J Physiol. 1969 Sep;204(1):31-50.

The iodide space in rabbit brain varies greatly depending on the conditions under which it is
determined."

"When 131I- only is used the iodide space 4 hr after administration of the marker is of the order of
2%. The iodide content of the cerebrospinal fluid (c.s.f.) is about 1% of that of the serum."

"Depression of the active iodide transport by perchlorate increases the space to 8·2% and the
iodide content of the c.s.f. to 26% of that of the serum."

"The active iodide transport can also be depressed by saturation with unlabelled iodide. Up to a
serum iodide concentration of 5 mM the space determined after 5 hr remained constant at 2·7%.
The iodide space grew when the serum iodide content was enhanced from 5 to 20 mM, to become
constant at a value of 10·6% on further increase of the serum iodide (up to 50 mM). The iodide
content of the c.s.f. increased in a similar manner as the space with the iodide concentration of the
serum to about 1/3 of the serum concentration. The iodide space of the muscle was independent of
the plasma iodide content."

"From 4 to 8 hr after administration of 131I- alone or with unlabelled iodide (to a serum concentration
of 15 mM) the iodide space remained relatively constant."

"When 131I- was administered in the fluid with which the ventricles were perfused an iodide space of
about 7% was attained after about 5 hr."

"In experiments in which 131I- was administered intravenously and the sink action of the c.s.f. was
eliminated by perfusion of the ventricles with a perfusate containing as much 131I- as the plasma,
the iodide space was 10·2%. When in addition active iodide transport was depressed by perchlorate
the space increased to 16·8%."

"Intravenous administration of labelled and unlabelled iodide (to a serum concentration of 20-40 mM)
and ventricle perfusion with the same concentration of 131I- and unlabelled iodide as in the plasma
yielded an iodide space of 20·8%. In similar experiments the iodide concentration of the perfusate
was so adjusted that after 5 hr perfusion its iodide content hardly changed during the passage
through the ventricles. Under these conditions the iodide concentration of the extracellular and
perfusion fluids can be considered to be near equal. The iodide space computed on the basis of the
iodide content of the outflowing fluid was 22·5%."

"The large iodide space could be equated with the extracellular space if the iodide remained
extracellular. This seems to be the case in the muscle where the iodide space is similar to the inulin
space."

"The large effects on the iodide space of perchlorate and saturation with unlabelled iodide in
experiments in which the marker was administered intravenously and in the perfusate (7 and 8)
suggests the presence of an active iodide transport from the brain extracellular fluid into the blood
over the blood—brain barrier.


ANDRASI
Determination of iodine in human brain by epithermal and radiochemical neutron activation analysis
Andrasi E, Kucera J, Belavari C, Mizera J
Microchemical Journal 2007.  85: 157-163.

Despite the role of iodine for proper development of the brain and the functions of the element, the
accurate data on its concentration in brain tissue are largely lacking, the main reason being
analytical difficulties associated with determination of the element especially at low levels.  In this
work, samples from human brain regions from Hungarian patients were analyzed using epithermal
and radiochemical neutron activation analysis (ENAA and RNAA, respectively).  The RNAA
procedure is based on alkaline-oxidative fusion followed by extraction of elemental iodine in
chloroform.  The results were checked by the analysis of biological standard reference materials,
namely bovine liver, bone meal and diet, and by comparison with previous results obtained by a
different RNAA procedure.

Iodine concentration in different human brain parts.
Andrasi E, Belavari C, Stibilj V, Dermelj M, Gawlik D.
Anal Bioanal Chem. 2004 Jan;378(1):129-33. Epub 2003 Nov 13.
[abstract only]

Iodine is one of the most important essential elements as demonstrated by the fact that its deficiency
can cause goitre. Nevertheless, quantitative data on its concentration in biological materials,
especially in the human brain, are scarce. There is therefore a demand for accurate and reliable
information on iodine in these types of samples. The purpose of the present work was to determine
the concentration of total iodine in some control human brain parts by rapid radiochemical neutron
activation analysis. Our second goal was to determine I distribution between lipid fraction and in
brain tissue without lipid by applying two types of solvent extraction methods. The results were
checked by the analysis of biological standard reference materials with certified or literature values
for iodine and good agreement was found.

Normal Human Brain Analysis.
E Andrasi, L Orosz, L Bezur, L Ernyei, Z Molnar
Microchemical J, 1995.  pp. 99-105.
[citation only]



Becker
Cerebrospinal fluid iodide.
Becker B
Am J Physiol. 1961 Dec;201:1149-51.
[abstract only]

In vitro preparations of rabbit choroid plexus accumulated I131 to a concentration 20–30 times the
media. The accumulation was temperature dependent and was blocked by metabolic inhibitors. It
could also be saturated with iodide, and was inhibited by perchlorate, fluoroborate, and related
anions. In vivo the low 4-hr steady state concentration (1.6% of plasma) of trace doses of I131 in the
rabbit cerebrospinal fluid was increased (to 40% of plasma) by the systemic administration of iodide
or perchlorate. The results resembled qualitatively those obtained in the vitreous and aqueous
humors of the same animals and suggested an active transport of iodide out of the cerebrospinal
fluid, much as postulated previously for ocular fluids.



Bernal
Iodine and brain development.
Bernal J.
Biofactors. 1999;10(2-3):271-6. Review.
[abstract only]

The development of the brain is critically dependent on an adequate supply of iodine. Iodine is an
integral part of thyroid hormone, which acts on brain development by regulating the expression of
target genes. The active thyroid hormone, T3, is generated in part in the thyroid gland, but about
80% of T3 in brain is formed locally from T4 deiodination mainly by the action of a specific
iodothyronine deiodinase. This enzyme is highly expressed in astrocytes, which take up T4 from the
blood and deliver T3 for neuronal use. In the target cells T3 binds to nuclear receptors which are
transcription factors. The T3 receptors are expressed in the brain before fetal thyroid gland function
and may be activated by maternal thyroid hormone during midgestation. Although a group of thyroid
hormone target genes has been identified in recent years, many basic questions of thyroid hormone
action in the brain remain to be elucidated.

Thyroid hormones and brain development.
Bernal J.
Vitam Horm. 2005;71:95-122. Review.
[abstract only]

The action of thyroid hormones (thyroxine, T4; triiodothyronine, T3) on brain development and
function is gaining renewed interest. It has been known for many years that thyroid hormones are
very important in mammalian brain maturation, influencing many aspects related to neural cell
migration, differentiation, and signaling. In the last 10 years, genes regulated by thyroid hormones
have been identified in the rodent brain, and understanding of the role of thyroid hormone nuclear
receptors has been facilitated with the analysis of the phenotype of mutant mice for the different
receptor isoforms. The general picture that emerges is that T4 and T3 may enter the brain through
specific transporters. T4 is converted to the active hormone, T3, in glial cells, astrocytes, and
tanycytes, although the main target cells are neurons and maturing oligodendrocytes. T3, acting
through the nuclear receptors, controls the expression of genes involved in myelination, cell
differentiation, migration, and signaling. In addition to transducing the T3 signal, the nuclear
receptors also have activity in the unliganded state (i.e., as aporeceptors), mainly as repressors of
transcription. The physiological meaning of aporreceptor action is not known, but they may play a
role in the genesis of the hypothyroid phenotype. Among the questions that remain to be explored in
more detail is the role of thyroid hormones and the T3 receptors, both liganded and unliganded, in
the fetal brain, especially before onset of fetal thyroid gland function. These questions are relevant
for human health and the management of thyroid diseases during pregnancy.

The significance of thyroid hormone transporters in the brain.
Bernal J.
Endocrinology. 2005 Apr;146(4):1698-700.

The developing brain is an important target of thyroid hormones. A complex regulatory network
involving transfer of thyroid hormones through the brain barriers, interactions between neurons and
glial cells, and deiodinase expression, works to deliver the appropriate amount of T3 to the nuclear
receptors. The data provided by Heuer et al. in this issue indicates that specific thyroid hormone
transporters may also be an essential part of this regulatory system.



Bito
Factors affecting the distribution of iodide and bromide in the central nervous system.
Bito LZ, Bradbury MW, Davson H.
J Physiol. 1966 Jul;185(2):323-354.

1. Even when a steady level of (131)I(-) is maintained in the blood for long periods, the uptake by
brain and spinal cord is very small, and the possibility that this is due to an active transport of I(-)
from brain-tissue to blood has been examined.

2. Most of the phenomena, however, can be explained on the basis of a slow passive diffusion
across the blood-brain barrier associated with an active transport of (131)I(-) out of the c.s.f. across
the choroid plexuses, so that, except possibly for the spinal cord, active transport from central
nervous parenchyma into the blood need not be postulated. If it does occur, it contributes very little
to the net exchanges between the three compartments, plasma, c.s.f. and extracellular fluid.

3. The steady-state distribution of bromide between plasma and c.s.f. is normally such that the
concentration in the c.s.f. is only some 70% of that in plasma; it has been shown that this is most
probably due to an active transport of Br(-) across the choroid plexuses