ArticleEnvironmental health perspectives2019
Influence of Nanomolar Deltamethrin on the Hallmarks of Primary Cultured Cortical Neuronal Network and the Role of Ryanodine Receptors.
Article in Environmental health perspectives, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed, 27 citations in OpenAlex.
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- The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation.Bioengineered · 2021Article
- TRPV3 enhances skin keratinocyte proliferation through EGFR-dependent signaling pathways.Cell biology and toxicology · 2021Article
- Article
- Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish.Cardiovascular toxicology · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe pyrethroid deltamethrin (DM) is broadly used for insect control. Although DM hyperexcites neuronal networks by delaying inactivation of axonal voltage-dependent [Formula: see text] channels, this mechanism is unlikely to mediate neurotoxicity at lower exposure levels during critical perinatal periods in mammals.
objectivesWe aimed to identify mechanisms by which acute and subchronic DM altered axonal and dendritic growth, patterns of synchronous [Formula: see text] oscillations (SCOs), and electrical spike activity (ESA) functions critical to neuronal network formation.
methodsMeasurements of SCOs using [Formula: see text] imaging, ESA using microelectrode array (MEA) technology, and dendritic complexity using Sholl analysis were performed in primary murine cortical neurons from wild-type (WT) and/or ryanodine receptor 1 ([Formula: see text]) mice between 5 and 14 d in vitro (DIV). [Formula: see text] binding analysis and a single-channel voltage clamp were utilized to measure engagement of RyRs as a direct target of DM.
resultsNeuronal networks responded to DM ([Formula: see text]) as early as 5 DIV, reducing SCO amplitude and depressing ESA and burst frequencies by 60-70%. DM ([Formula: see text]) enhanced axonal growth in a nonmonotonic manner. [Formula: see text] enhanced dendritic complexity. DM stabilized channel open states of RyR1, RyR2, and cortical preparations expressing all three isoforms. DM ([Formula: see text]) altered gating kinetics of RyR1 channels, increasing mean open time, decreasing mean closed time, and thereby enhancing overall open probability. SCO patterns from cortical networks expressing [Formula: see text] were more responsive to DM than WT. [Formula: see text] neurons showed inherently longer axonal lengths than WT neurons and maintained less length-promoting responses to nanomolar DM.
conclusionsOur findings suggested that RyRs were sensitive molecular targets of DM with functional consequences likely relevant for mediating abnormal neuronal network connectivity in vitro. https://doi.org/10.1289/EHP4583.
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