Manganese toxicity is targeting an early step in the dopamine signal transduction pathway that controls lateral cilia activity in the bivalve mollusc Crassostrea virginica

Abstract

Manganese is a neurotoxin causing manganism, a Parkinson-like clinical disorder. Manganese has been shown to interfere with dopaminergic neurotransmission, but the neurotoxic mechanism involved is not fully resolved. In the bivalve mollusc Crassostrea virginica also known as the eastern oyster, beating rates of lateral cilia of the gill are controlled by dopaminergic-serotonergic innervation originating from their cerebral and visceral ganglia. Terminal release of dopamine activates D2-like receptors on these gill cells inhibiting adenylyl cyclase and slowing cilia beating rates. In C. virginica, manganese treatment disrupts this dopaminergic innervation of the gill, preventing the normal cilio-inhibitory response of lateral cells to dopamine. In this study an adenylyl cyclase activator (forskolin) and two different inhibitors (MDL-12,330A and SQ 22,536) were used to determine if manganese had any effects on the adenylyl cyclase step of the dopamine D2 receptor signal transduction pathway. The results showed that neither the adenylyl cyclase activator nor the inhibitors were affected by manganese in the control of lateral ciliary activity. This suggests that in C. virginica the mechanism of manganese toxicity on the dopaminergic control of lateral ciliary activity is targeting an early step in the D2R signal transduction pathway, which may involve interference with D2 receptor activation or alternatively some other downstream signaling activity that does not affect adenylyl cyclase.

Brain manganese and the balance between essential roles and neurotoxicity

“…Research has predominantly focused on DA subtype 2 receptor (D2R) and the DA transporter (DAT) responsible for Mn transport into DA neurons (100). Nelson et al showed that D2R are involved Mn toxicity, at the receptor level or at a point downstream in the signaling cascade that does not involve adenylyl cyclase (101). MnCl 2 exposure can lead to DA depletion and blunt the efficacy of DAergic neurotransmission leading to upregulation of the post-synaptic dopamine receptors and causing behavioral alterations including hypoactivity, cognitive impairments and altered sensorimotor function (102).…”

Environmental concentrations of Roundup in combination with chlorpromazine or heating causes biochemical disturbances in the bivalve mollusc Unio tumidus

“…Consequently, its input into the water runoff is expected to be enhanced. The biological effects of Cpz are associated with calcium homeostasis (Xu et al 2010 ) and manganese toxicity (Nelson et al 2018 ). The drug is known to interact with the cell membrane dynamin and block the clathrin-dependent endocytosis essential for the entry of coronavirus into the host cell (Plaze et al 2020 ).…”

Facile Strategy for Fabricating an Organosilica-Modified Fe3O4 (OS/Fe3O4) Hetero-nanocore and OS/Fe3O4@SiO2 Core–Shell Structure for Wastewater Treatment with Promising Recyclable Efficiency

“…The rapid pollution of water with heavy metals has become the most prevalent environmental concern. − Heavy metals may alter the water surface as a result of industrial activities which produce polluting effluents that are discharged to the water surface. , Heavy metals have a high ability for persistence and can be transferred to various environmental components, such as soil, plants, food, and drinking water. Human exposure to heavy metals, even with very low traces, is considered hazardous due to the fact that heavy metal accumulation, over time, can lead to higher and dangerous concentrations, and the symptoms start to appear late in the human lifecycle. − For example, manganese is considered as essential element for humans; however, the reported risk of manganese pollution is now reaching higher levels, especially among people who drink manganese-polluted water or those who work in mining and are exposed to air polluted with manganese through direct inhalation. − The commonly reported health effects of excessive exposure to manganese include depression, changes in memory ability, as well as irritability and, in some cases, tremors. , Another example of a heavy metal pollutant is cobalt, which is an essential element at trace levels but is toxic at higher levels of exposure, leading to hematological effects as well as immune system disturbance. − Lead is reported to have toxic effects on humans at high exposure levels in both children and adults. The symptoms include renal and degenerative effects as well as intellectual disabilities. − There are many treatment methods for the remediation of heavy metals from wastewater, such as reverse osmosis, chemical precipitation, ion exchange, filtration, and adsorption. ,− …”

“… 12 − 14 The commonly reported health effects of excessive exposure to manganese include depression, changes in memory ability, as well as irritability and, in some cases, tremors. 15 , 16 Another example of a heavy metal pollutant is cobalt, which is an essential element at trace levels but is toxic at higher levels of exposure, leading to hematological effects as well as immune system disturbance. 17 − 20 Lead is reported to have toxic effects on humans at high exposure levels in both children and adults.…”