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Early Synaptic Alterations and Selective Adhesion Signaling in Hippocampal Dendritic Zones Following Organophosphate Exposure
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Organophosphates account for many of the world’s deadliest poisons. They inhibit acetylcholinesterase causing cholinergic crises that lead to seizures and death, while survivors commonly experience long-term neurological problems. Here, we treated brain explants with the organophosphate compound paraoxon and uncovered a unique mechanism of neurotoxicity. Paraoxon-exposed hippocampal slice cultures exhibited progressive declines in synaptophysin, synapsin II, and PSD-95, whereas reduction in GluR1 was slower and NeuN and Nissl staining showed no indications of neuronal damage. The distinctive synaptotoxicity was observed in dendritic zones of CA1 and dentate gyrus. Interestingly, declines in synapsin II dendritic labeling correlated with increased staining for β1 integrin, a component of adhesion receptors that regulate synapse maintenance and plasticity. The paraoxon-induced β1 integrin response was targeted to synapses, and the two-fold increase in β1 integrin was selective as other synaptic adhesion molecules were unchanged. Additionally, β1 integrin–cofilin signaling was triggered by the exposure and correlations were found between the extent of synaptic decline and the level of β1 integrin responses. These findings identified organophosphate-mediated early and lasting synaptotoxicity which can explain delayed neurological dysfunction later in life. They also suggest that the interplay between synaptotoxic events and compensatory adhesion responses influences neuronal fate in exposed individuals.
- Subjects :
- 0301 basic medicine
lcsh:Medicine
Nerve Tissue Proteins
Hippocampal formation
Hippocampus
Article
Paraoxon
Synapse
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Animals
lcsh:Science
Neural Cell Adhesion Molecules
Multidisciplinary
biology
Cell adhesion molecule
Dentate gyrus
Integrin beta1
lcsh:R
Antigens, Nuclear
Synapsin
Dendrites
Environmental Exposure
Synapsins
Acetylcholinesterase
Cellular neuroscience
Organophosphates
Rats
030104 developmental biology
chemistry
nervous system
Synapses
biology.protein
Synaptophysin
Extracellular signalling molecules
lcsh:Q
Cholinesterase Inhibitors
NeuN
Neuroscience
Disks Large Homolog 4 Protein
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....c52e797a1c71aceea9a5feb7b809eafe