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Nanoparticles are very small particles of between 1-100 nanometres in size. They are used in drug delivery, chemotherapy, imaging and diagnostics because of their ability to travel within organisms by utilising cellular pathways. During their interactions with cell membranes and internalisation into cells, key signalling pathways and processes are altered. The internalisation of nanoparticles can also detrimentally affect neighbouring cells in a manner similar to the radiation-induced bystander effect.
Scientists grew a layer of BeWo cells- a cell type used to model the placental barrier, in a laboratory on a porous membrane. This cell barrier was exposed to cobalt chromium nanoparticles and the media under the barrier was later collected and transferred onto cultures of human brain cells, which sustained DNA damage. Confirmatory exposures to maternal mice during embryonic development were also performed that also found exposures resulted in damage to DNA in the hippocampus of the newborn offspring.
Cells in the barriers, processed the nanoparticles by a natural cellular pathway- autophagy, leading to those cells generating signaling molecules. These signaling molecules caused DNA damage to the brain cells astrocytes and neurons; this was confirmed as when either autophagy or IL-6 (main cell messenger identified) was blocked, the amount of DNA damage was reduced. These findings support the idea that indirect effects of nanoparticles on cells which is the case in this study might be as important to consider as their direct effects when evaluating their safety Importantly.
The DNA damage to neurons was dependant on astrocytes being present. Astrocytes are the most common cell type in the brain that have multiple roles in the brain and can have both positive and negative effects on neighbouring neurons. According to Maeve Caldwell, Professor in Neuroscience at Trinity College Dublin, lead author on the study, “Astrocytes are the most common cell type in the brain which for many years were considered to play a supportive role to neurons.
Media from nanoparticle-exposed cellular barriers only damaged neurons when astrocytes were present, provides further evidence that the role of astrocytes in the brain goes way beyond that of providing support to neurons. When astrocytes are stressed under experimental conditions, they are capable of damaging neighbouring neurons. This could have implications for developing understanding of how astrocyte behaviour may affect neuronal health in many neurodegenerative conditions like Alzheimer’s and Parkinson’s disease. These shows nanoparticle damage to brain cells can cause DNA damage that’s dependent on astrocytes.
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