Metallothionein expression in the central nervous system in response to chronic heavy metal exposure: possible neuroprotective mechanism.

It has been reported that volcanoes release several tonnes of mercury per year among other heavy metals through eruptions, fumaroles, or diffuse soil degassing. Since a high percentage of the world's population lives in the vicinity of an active volcano, the aim of this study is to evaluate the accumulation of these metals in the central nervous system and the presence of cellular mechanisms of heavy metal detoxification such as metallothioneins. To carry out this study, wild mice (Mus musculus) chronically exposed to an active volcanic environment were captured in Furnas village (Azores, Portugal) and compared with those trapped in a reference area (Rabo de Peixe, Azores, Portugal). On the one hand, the heavy metal load has been evaluated by analyzing brain and cerebellum using ICP-MS and a mercury analyzer and on the other hand, the presence of metallothionein 2A has been studied by immunofluorescence assays. Our results show a higher load of metals such as mercury, cadmium and lead in the central nervous system of exposed mice compared to non-exposed individuals and, in addition, a higher immunoreactivity for metallothionein 2A in different areas of the cerebrum and cerebellum indicating a possible neuroprotection process.

Epithelial morphometric alterations and mucosecretory responses in the nasal cavity of mice chronically exposed to hydrothermal emissions.

Air pollutants (either of natural or anthropogenic origin) represent a considerable environmental risk to human health by affecting the respiratory system and causing respiratory disorders. In this study, we investigate the effects of chronic exposure to hydrothermal emissions on the nasal cavity of mice since it is the first and the most exposed region of the respiratory system. This study, carried in S. Miguel Island, Azores-Portugal, used Mus musculus as a bioindicator species. Mice were captured in an area with non-eruptive active volcanism (Furnas Village) and another area without volcanism (Rabo de Peixe, reference site). The hydrothermal emissions present at Furnas Village are characterized by the continuous release of several gases (CO2, H2S, 222Rn) along with metals (e.g. Hg, Cd, Zn, Al) and particulate matter into the environment. We test the hypothesis whether chronic exposure to this specific type of pollution causes epithelial morphometric, mucosecretory and neuronal alterations on the nasal cavity. Thickness measurements were taken in the squamous, respiratory and olfactory epithelia. The relative density of cell types (basal, support and neurons) was also assessed in the olfactory epithelium and the mucosecretory activity was determined in the lateral nasal glands, Bowman's gland and goblet cells. Mice chronically exposed to hydrothermal emissions presented thinner olfactory epithelia and lesser mucous production, which could result in loss of olfactory capabilities as well as a decrease in the protective function provided by the mucous to the lower respiratory tract. For the first time, it is demonstrated that, in mice, this specific type of non-eruptive active volcanism causes epithelial and mucosecretory alterations, leading to the loss of olfactory capabilities.

Occurrence of Volcanogenic Inorganic Mercury in Wild Mice Spinal Cord: Potential Health Implications.

Mercury accumulation has been proposed as a toxic factor that causes neurodegenerative diseases. However, the hazardous health effects of gaseous elemental mercury exposure on the spinal cord in volcanic areas have not been reported previously in the literature. To evaluate the presence of volcanogenic inorganic mercury in the spinal cord, a study was carried out in São Miguel island (Azores, Portugal) by comparing the spinal cord of mice exposed chronically to an active volcanic environment (Furnas village) with individuals not exposed (Rabo de Peixe village), through the autometallographic silver enhancement histochemical method. Moreover, a morphometric and quantification analysis of the axons was carried out. Results exhibited mercury deposits at the lumbar level of the spinal cord in the specimens captured at the site with volcanic activity (Furnas village). A decrease in axon calibre and axonal atrophy was also observed in these specimens. Given that these are relevant hallmarks in the neurodegenerative pathologies, our results highlight the importance of the surveillance of the health of populations chronically exposed to active volcanic environments.

The Health Hazards of Volcanoes: First Evidence of Neuroinflammation in the Hippocampus of Mice Exposed to Active Volcanic Surroundings.

Neuroinflammation is a process related to the onset of neurodegenerative diseases; one of the hallmarks of this process is microglial reactivation and the secretion by these cells of proinflammatory cytokines such as TNFα. Numerous studies report the relationship between neuroinflammatory processes and exposure to anthropogenic air pollutants, but few refer to natural pollutants. Volcanoes are highly inhabited natural sources of environmental pollution that induce changes in the nervous system, such as reactive astrogliosis or the blood-brain barrier breakdown in exposed individuals; however, no neuroinflammatory event has been yet defined. To this purpose, we studied resting microglia, reactive microglia, and TNFα production in the brains of mice chronically exposed to an active volcanic environment on the island of São Miguel (Azores, Portugal). For the first time, we demonstrate a proliferation of microglial cells and an increase in reactive microglia, as well an increase in TNFα secretion, in the central nervous system of individuals exposed to volcanogenic pollutants.

Chronic exposure to volcanic gaseous elemental mercury: using wild Mus musculus to unveil its uptake and fate.

Volcanoes are a natural source of gaseous elemental mercury (GEM) (Hg0). Monitoring GEM releases of volcanic origin has been widely studied; however, few studies have been performed about the biomonitoring of species exposed to GEM, rendering an unknown risk to the worldwide populations living in the vicinity of an active volcano. In this pilot study, we used Mus musculus as a bioindicator species to understand to what extent lungs are the main route of mercury uptake in populations chronically exposed to active volcanic environments. Autometallographic silver protocol was used to detect mercury deposits in the histological lung slides. Abundant mercury deposits were found in the lungs of specimens captured at the site with volcanic activity (Furnas Village, S. Miguel Island-Azores). The presence of mercury in the lungs could represent not only hazardous effects to the lung itself but also to other tissues and organs, such as brain and kidneys. This study confirms that the main uptake route for GEM is the lungs and that, even at very low concentrations in the environment, a chronic exposure to Hg0 results in its bioaccumulation in the lung tissue. These results reinforce that biomonitoring studies should be combined with monitoring classical approaches in order to better characterize the risks of exposure to Hg0 in volcanic environments.

First report on the prevalence of Klossiella muris in Mus musculus for S. Miguel Island - Azores (Portugal).

Klossiella is a genus of apicomplexan coccidian parasites with a global distribution, whose members typically infect the renal tissue of a wide variety of vertebrate hosts with a high level of host specificity. The presence of this parasite has been previously associated with kidney inflammatory processes. To our knowledge, this is the first report on the prevalence of Klossiella muris in the house mouse (Mus musculus) in Portugal (São Miguel Island - Azores). The prevalence of K. muris was determined through histopathological examination of renal tissue collected during necropsy of 130 mice captured between the years of 2011-2019. K. muris was diagnosed in 45.38% (CI95: 40.9-85.4) of the examined mice. Infection with this parasite was associated with mild to severe kidney inflammation, assessed by the presence of inflammatory processes in the renal cortex and medulla. CAPSULE: First record on coccidiosis caused by infection of Klossiella muris in Mus musculus in Portugal.

First record on mercury accumulation in mice brain living in active volcanic environments: a cytochemical approach.

The health effects of mercury vapor exposure on the brain in volcanic areas have not been previously addressed in the literature. However, 10% of the worldwide population inhabits in the vicinity of an active volcano, which are natural sources of elemental mercury emission. To evaluate the presence of mercury compounds in the brain after chronic exposure to volcanogenic mercury vapor, a histochemical study, using autometallographic silver, was carried out to compare the brain of mice chronically exposed to an active volcanic environment (Furnas village, Azores, Portugal) with those not exposed (Rabo de Peixe village, Azores, Portugal). Results demonstrated several mercury deposits in blood vessels, white matter and some cells of the hippocampus in the brain of chronically exposed mice. Our results highlight that chronic exposure to an active volcanic environment results in brain mercury accumulation, raising an alert regarding potential human health risks. These findings support the hypothesis that mercury exposure can be a risk factor in causing neurodegenerative diseases in the inhabitants of volcanically active areas.

Reactive astrogliosis in the dentate gyrus of mice exposed to active volcanic environments.

Air pollution has been associated with neuroinflammatory processes and is considered a risk factor for the development of neurodegenerative diseases. Volcanic environments are considered a natural source of air pollution. However, the effects of natural source air pollution on the central nervous system (CNS) have not been reported, despite the fact that up to 10% of the world's population lives near a historically active volcano. In order to assess the response of the CNS to such exposure, our study was conducted in the island of Sao Miguel (Azores, Portugal) in two different areas: Furnas, which is volcanically active one, and compared to Rabo de Peixe, a reference site without manifestations of active volcanism using Mus musculus as a bioindicator species. To evaluate the state of the astroglial population in the dentate gyrus in both samples, the number of astrocytes was determined using immunofluorescence methods (anti-GFAP and anti-GS). In addition, the astrocytic branches in that hippocampal area were examined. Our results showed an increase in GFAP+ astrocytes and a reduction in GS+ astrocytes in Furnas-exposed mice compared to animals from Rabo de Peixe. In addition, astrocytes in the dentate gyrus of chronically exposed animals exhibited longer branches compared to those residing at the reference site. Thus, reactive astrogliosis and astrocyte dysfunction are found in mice living in an active volcanic environment.

Chronic exposure to non-eruptive volcanic activity as cause of bronchiolar histomorphological alteration and inflammation in mice.

It is estimated that 10% of the worldwide population lives in the vicinity of an active volcano. However, volcanogenic air pollution studies are still outnumbered when compared with anthropogenic air pollution studies, representing an unknown risk to human populations inhabiting volcanic areas worldwide. This study was carried out in the Azorean archipelago of Portugal, in areas with active non-eruptive volcanism. The hydrothermal emissions within the volcanic complex of Furnas (São Miguel Island) are responsible for the emission of nearly 1000 tons of CO2 per day, along with H2S, the radioactive gas - radon, among others. Besides the gaseous emissions, metals (e.g., Hg, Cd, Al, Ni) and particulate matter are also released into the environment. We test the hypothesis that chronic exposure to volcanogenic air pollution alters the histomorphology of the bronchioles and terminal bronchioles, using the house mouse, Mus musculus, as bioindicator species. Mus musculus were live-captured at three different locations: two villages with active volcanism and a village without any type of volcanic activity (reference site). The histomorphology of the bronchioles (diameter, epithelium thickness, smooth muscle layer thickness, submucosa thickness and the histological evaluation of the peribronchiolar inflammation) and of the terminal bronchioles (epithelium thickness and classification) were evaluated. Mice chronically exposed to volcanogenic air pollution presented bronchioles with increased epithelial thickness, increased smooth muscle layer, increased submucosa thickness and increased peribronchiolar inflammation. Similarly, terminal bronchioles presented structural alterations consistent with bronchodysplasia. For the first time we demonstrate that chronic exposure to non-eruptive volcanically active environments causes inflammation and histomorphological alterations in mice lower airways consistent with asthma and chronic bronchitis. These results reveal that chronic exposure to non-eruptive volcanic activity represents a risk factor that can affect the health of the respiratory system of humans inhabiting hydrothermal areas.

Overproduction of TNF-α and lung structural remodelling due to chronic exposure to volcanogenic air pollution.

Volcanogenic air pollution studies and their effects on the respiratory system are still outnumbered by studies regarding the effects of anthropogenic air pollution, representing an unknown risk to human population inhabiting volcanic areas worldwide (either eruptive or non-eruptive areas). This study was carried in the archipelago of the Azores- Portugal, in two areas with active volcanism (Village of Furnas and Village of Ribeira Quente) and a reference site (Rabo de Peixe). The hydrothermal volcanism of Furnas volcanic complex is responsible for the release of 1000 t d-1 of CO2, H2S, the radioactive gas - radon, among others. Besides the gaseous emissions, particulate matter and metals (Hg, Cd, Zn, Al, Ni, etc.) are also released into the environment. We tested a hypothesis whether chronic exposure to volcanogenic air pollution causes lung structural remodelling, in the house mouse, Mus musculus, as a bioindicator species. Histopathological evaluations were performed to assess the amount of macrophages, mononuclear leukocyte infiltrate, pulmonary emphysema, and the production of pro-inflammatory cytokine TNF-α. Also, the percentage of collagen and elastin fibers was calculated. Mice chronically exposed to volcanogenic air pollution presented an increased score in the histopathological evaluations for the amount of macrophages, mononuclear leukocyte infiltrate, pulmonary emphysema and production of TNF-α; and also increased percentages of collagen and elastin. For the first time, we demonstrate that non-eruptive active volcanism has a high potential to cause lung structural remodelling. This study also highlights the Mus musculus as a useful bioindicator for future biomonitoring programs in these type of volcanic environments.