Though environmental factors are linked to neurodegenerative diseases, the exact cause and mechanism remain still unclear. But a new research throws light on the relationship by revealing that environmental factors, including pesticides, can have an effect on the genes, triggering changes similar to that of autism and Alzheimer's disease.
The study published in the Nature Communications
was done by researchers at the University of North Carolina (UNC), who conducted experiments on mouse genes by exposing them to various fungicides and pesticides commonly used in agriculture.
‘A class of commonly used fungicides called strobilurins produce gene expression changes similar to those in people with autism and neurodegenerative conditions, including Alzheimer's disease and Huntington's disease.’
The brain cells of the mice were exposed to hundreds of pesticides and the neuronal changes were studied. They found six different transcriptional changes, of which one was associated with changes related to neurodegenerative diseases.
"Based on RNA sequencing, we describe six groups of chemicals. We found that chemicals within each group altered expression in a common manner. One of these groups of chemicals altered the levels of many of the same genes that are altered in the brains of people with autism or Alzheimer's disease," said Dr. Mark Zylka, lead author of the study.
A class of pesticides called 'strobilurins' that include fenamidone, pyraclostrobin, famoxadone, trifloxystrobin altered the mitochondria by disrupting the activity of genes involved in synaptic transmission. Further analysis showed that these pesticides increased free radical production inside the mitochondria.
A pesticide called rotenone linked to Parkinson's disease showed to induce free radicals to destabilize microtubules. Microtubules are structures that help in transportation of organelles inside the cell. Researchers found that destabilization of microtubules triggered the swelling of neurons, which is associated with problems in brain development and with neurodegeneration. Disruption of cytoskeletal function has been implicated in autism.
"We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age, and neurodegeneration. These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane," said the authors.
The team also found that pesticides induced neuroinflammation that has been linked to various neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease.
Dr. Zylka cautioned, "It is too early to say whether these chemicals cause these conditions in people. Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain."
Reference: Brandon L. Pearson, Jeremy M. Simon, Eric S. McCoy, Gabriela Salazar, Giulia Fragola & Mark J. Zylka, Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration, Nature Communications 2016, doi:10.1038/ncomms11173.