Increasingly, exposure to various chemicals found in our environment has
been found to be a significant contributor to the risk of developing
neurological disease, such as Parkinson disease, autism spectrum
disorder, as well as other deficits in thought and function. Exposure to
these compounds during critical periods of neurodevelopment,
encompassing exposures that occur in utero, during infancy,
childhood, and adolescence, represents a time period of nervous system
growth that is uniquely vulnerable to disruption by environmental
chemicals. Indeed, a contemporary hypothesis suggests that the
pathological cascade associated with many common neurological disorders
has its origin in disturbances of normal neurodevelopment. Moreover,
alterations to the ontogeny of the synapse and neurotransmitter
signaling during neurodevelopment may be a premier pathological event
that underlies neuropsychiatric and neurodegenerative disease. To
interrogate the impact of exposure to a ubiquitous environmental
chemical, the pesticide, endosulfan, on development of neurotransmitter
circuits, we coupled in vitro and in vivo platforms to
evaluate its effect on the formation of GABAergic, glutamatergic, and
dopaminergic pathways in the frontal cortex. With this approach we found
exposure of cortical neurons, in vitro, exhibited a marked
reduction in the length of their neurite process as well as the number
of synaptic connections. Further investigation using an in vivo
model of developmental exposure identified significant alterations to
pre and postsynaptic proteins involved in neurotransmitter handling and
signaling in each of the neurotransmitter systems investigated. These
findings suggest that exposure to endosulfan during vulnerable periods
of neurodevelopment can alter the normal development and potential
function of neurotransmission in the frontal cortex. Interestingly, the
alterations identified in our study closely mimic the pathological
markers associated with schizophrenia, which shows disturbances in
synaptic proteins important for GABAergic, glutamatergic, and
dopaminergic signaling in the frontal cortex. These findings provide
important support for the impact of exposure to environmental chemicals
during neurodevelopment and risk for neurological disease.
been found to be a significant contributor to the risk of developing
neurological disease, such as Parkinson disease, autism spectrum
disorder, as well as other deficits in thought and function. Exposure to
these compounds during critical periods of neurodevelopment,
encompassing exposures that occur in utero, during infancy,
childhood, and adolescence, represents a time period of nervous system
growth that is uniquely vulnerable to disruption by environmental
chemicals. Indeed, a contemporary hypothesis suggests that the
pathological cascade associated with many common neurological disorders
has its origin in disturbances of normal neurodevelopment. Moreover,
alterations to the ontogeny of the synapse and neurotransmitter
signaling during neurodevelopment may be a premier pathological event
that underlies neuropsychiatric and neurodegenerative disease. To
interrogate the impact of exposure to a ubiquitous environmental
chemical, the pesticide, endosulfan, on development of neurotransmitter
circuits, we coupled in vitro and in vivo platforms to
evaluate its effect on the formation of GABAergic, glutamatergic, and
dopaminergic pathways in the frontal cortex. With this approach we found
exposure of cortical neurons, in vitro, exhibited a marked
reduction in the length of their neurite process as well as the number
of synaptic connections. Further investigation using an in vivo
model of developmental exposure identified significant alterations to
pre and postsynaptic proteins involved in neurotransmitter handling and
signaling in each of the neurotransmitter systems investigated. These
findings suggest that exposure to endosulfan during vulnerable periods
of neurodevelopment can alter the normal development and potential
function of neurotransmission in the frontal cortex. Interestingly, the
alterations identified in our study closely mimic the pathological
markers associated with schizophrenia, which shows disturbances in
synaptic proteins important for GABAergic, glutamatergic, and
dopaminergic signaling in the frontal cortex. These findings provide
important support for the impact of exposure to environmental chemicals
during neurodevelopment and risk for neurological disease.
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