Mercury in the human adrenal medulla could contribute to increased plasma noradrenaline in aging.

Plasma noradrenaline levels increase with aging, and this could contribute to the sympathetic overactivity that is associated with essential hypertension and the metabolic syndrome. The underlying cause of this rise in noradrenaline is unknown, but a clue may be that mercury increases noradrenaline output from the adrenal medulla of experimental animals. We therefore determined the proportion of people from 2 to 104 years of age who had mercury in their adrenal medulla.

The distribution of toxic metals in the human retina and optic nerve head: Implications for age-related macular degeneration.

Objective: Toxic metals are suspected to play a role in the pathogenesis of age-related macular degeneration. However, difficulties in detecting the presence of multiple toxic metals within the intact human retina, and in separating primary metal toxicity from the secondary uptake of metals in damaged tissue, have hindered progress in this field. We therefore looked for the presence of several toxic metals in the posterior segment of normal adult eyes using elemental bioimaging.

Concentrations of toxic metals and essential trace elements vary among individual neurons in the human locus ceruleus.

Objective: Damage to locus ceruleus neurons could play a part in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis because of impairment of the blood-brain barrier and enhanced neuroinflammation. The locus ceruleus has connections throughout the brain and spinal cord, so the characteristic widespread multifocal pathology in these disorders could be due to damage to different subsets of locus ceruleus neurons. Previous studies have shown that only certain locus ceruleus neurons accumulate the neurotoxic metal mercury.

Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei.

Objective: Interference with the transmission of sensory signals along visual and auditory pathways has been implicated in the pathogenesis of hallucinations. The relay centres for vision (the lateral geniculate nucleus) and hearing (the medial geniculate nucleus) appear to be susceptible to the uptake of circulating mercury. We therefore investigated the distribution of mercury in cells of both these geniculate nuclei.

Elemental bioimaging shows mercury and other toxic metals in normal breast tissue and in breast cancers.

Objective: Exposure to toxic metals such as mercury has been proposed to be a risk factor for the development of breast cancer since some metals can promote genetic mutations and epigenetic changes. We sought to find what toxic metals are present in normal breast tissue and in the tumours of women who had mastectomies for invasive ductal breast carcinoma.

Materials And Methods: Formalin-fixed paraffin-embedded blocks from mastectomies for breast carcinoma were examined from 50 women aged 34-69 years.

The nitroxide 4-methoxy-tempo inhibits the pathogenesis of dextran sodium sulfate-stimulated experimental colitis.

Inflammatory bowel disease (IBD) is a chronic condition characterised by leukocyte recruitment to the gut mucosa. Leukocyte myeloperoxidase (MPO) produces the two-electron oxidant hypochlorous acid (HOCl), damaging tissue and playing a role in cellular recruitment, thereby exacerbating gut injury. We tested whether the MPO-inhibitor, 4-Methoxy-TEMPO (MetT), ameliorates experimental IBD.

Mercury in the retina and optic nerve following prenatal exposure to mercury vapor.

Damage to the retina and optic nerve is found in some neurodegenerative disorders, but it is unclear whether the optic pathway and central nervous system (CNS) are affected by the same injurious agent, or whether optic pathway damage is due to retrograde degeneration following the CNS damage. Finding an environmental agent that could be responsible for the optic pathway damage would support the hypothesis that this environmental toxicant also triggers the CNS lesions. Toxic metals have been implicated in neurodegenerative disorders, and mercury has been found in the retina and optic nerve of experimentally-exposed animals.

Mercury Is Taken Up Selectively by Cells Involved in Joint, Bone, and Connective Tissue Disorders.

The causes of most arthropathies, osteoarthritis, and connective tissue disorders remain unknown, but exposure to toxic metals could play a part in their pathogenesis. Human exposure to mercury is common, so to determine whether mercury could be affecting joints, bones, and connective tissues we used a histochemical method to determine the cellular uptake of mercury in mice. Whole neonatal mice were examined since this allowed histological assessment of mercury in joint, bone, and connective tissue cells.

Elemental Analysis of Aging Human Pituitary Glands Implicates Mercury as a Contributor to the Somatopause.

Growth hormone levels often decline on aging, and this "somatopause" is associated with muscle and bone loss, visceral adiposity and impaired cardiovascular function. Mercury has been detected in human pituitary glands, so to see if mercury could play a part in the somatopause we measured the proportion of people at different ages who had mercury in their anterior pituitary cells. Paraffin sections of pituitary glands taken at autopsy from 94 people between the ages of 2 and 99 years were stained for inorganic mercury using autometallography.

Age-related accumulation of toxic metals in the human locus ceruleus.

Damage to the locus ceruleus has been implicated in the pathogenesis of a number of neurological conditions. Locus ceruleus neurons accumulate toxic metals such as mercury selectively, however, the presence of toxic metals in locus ceruleus neurons of people of different ages, and with a variety of disorders, is not known. To demonstrate at what age toxic metals are first detectable in the locus ceruleus, and to evaluate whether their presence is more common in certain clinicopathological conditions, we looked for these metals in 228 locus ceruleus samples.

Inorganic mercury in human astrocytes, oligodendrocytes, corticomotoneurons and the locus ceruleus: implications for multiple sclerosis, neurodegenerative disorders and gliomas.

Neurotoxic metals have been implicated in the pathogenesis of multiple sclerosis, neurodegenerative disorders and brain tumours but studies of the location of heavy metals in human brains are rare. In a man who injected himself with metallic mercury the cellular location of mercury in his brain was studied after 5 months of continuous exposure to inorganic mercury arising from metallic mercury deposits in his organs. Paraffin sections from the primary motor and sensory cortices and the locus ceruleus in the pons were stained with autometallography to detect inorganic mercury and combined with glial fibrillary acidic protein immunohistochemistry to identify astrocytes.

Age-Related Uptake of Heavy Metals in Human Spinal Interneurons.

Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage.

Locus ceruleus neurons in people with autism contain no histochemically-detectable mercury.

Exposure to environmental mercury has been proposed to play a part in autism. Mercury is selectively taken up by the human locus ceruleus, a region of the brain that has been implicated in autism. We therefore looked for the presence of mercury in the locus ceruleus of people who had autism, using the histochemical technique of autometallography which can detect nanogram amounts of mercury in tissues.

Different Populations of Human Locus Ceruleus Neurons Contain Heavy Metals or Hyperphosphorylated Tau: Implications for Amyloid-β and Tau Pathology in Alzheimer's Disease.

A marked loss of locus ceruleus (LC) neurons is a striking pathological feature of Alzheimer's disease (AD). LC neurons are particularly prone to taking up circulating toxicants such as heavy metals, and hyperphosphorylated tau (tau(HYP)) appears early in these neurons. In an attempt to find out if both heavy metals and tau(HYP) could be damaging LC neurons, we looked in the LC neurons of 21 sporadic AD patients and 43 non-demented controls for the heavy metals mercury, bismuth, and silver using autometallography, and for tau(HYP) using AT8 immunostaining.

Heavy metals in locus ceruleus and motor neurons in motor neuron disease.

Background: The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls.

Uptake of inorganic mercury by human locus ceruleus and corticomotor neurons: implications for amyotrophic lateral sclerosis.

Background: Environmental toxins are suspected to play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In an attempt to determine which pathways these toxins can use to enter motor neurons we compared the distribution of mercury in the CNS of a human and of mice that had been exposed to inorganic mercury.

Results: In the human who had been exposed to metallic mercury, mercury was seen predominantly in the locus ceruleus and corticomotor neurons, as well as in scattered glial cells.

Inorganic mercury within motor neurons does not cause the TDP-43 changes seen in sporadic ALS.

Heavy metals have long been suspected to be involved in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS), but evidence for their toxic effects on motor neurons is limited. Characteristic mislocalisation of TDP-43 is seen in the motor neurons of patients with SALS, resulting in a lack of nuclear staining and cytoplasmic inclusions. To find out if a heavy metal can cause these TDP-43 changes, mice were exposed to varying doses of mercuric chloride or mercury vapor.

Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia.

The posterior cingulate cortex (PCC), a key component of the limbic system, has been implicated in the pathology of schizophrenia because of its sensitivity to NMDA receptor antagonists. Recent studies have shown that the PCC is dysfunctional in schizophrenia, and it is now suspected to be critically involved in the pathogenesis of schizophrenia. Studies also suggest that there are abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia.

Flaviviruses in motor neuron disease.

Sporadic motor neuron disease (MND) causes a progressive loss of motor neurons. West Nile virus can attack motor neurons, so we examined whether flavivirus infection could be detected in MND cases. Spinal cord sections from 22 MND cases were stained immunohistochemically with a flavivirus-specific antibody.

Zinc in the spinal cord of a mutant SOD1 mouse model of ALS.

Both decreases and increases in zinc have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We therefore examined the distribution of zinc in transgenic mutant superoxide dismutase 1 (SOD1) mice, a model for ALS. Frozen sections of spinal cord from these mice were stained for free zinc with autometallography.