Amphetamine Exposure during Embryogenesis Alters Expression and Function of Tyrosine Hydroxylase and the Vesicular Monoamine Transporter in Adult C. elegans.
Int J Mol Sci
; 25(8)2024 Apr 11.
Article
in En
| MEDLINE
| ID: mdl-38673805
ABSTRACT
Amphetamines (Amph) are psychostimulants broadly used as physical and cognitive enhancers. However, the long-term effects of prenatal exposure to Amph have been poorly investigated. Here, we show that continuous exposure to Amph during early development induces long-lasting changes in histone methylation at the C. elegans tyrosine hydroxylase (TH) homolog cat-2 and the vesicular monoamine transporter (VMAT) homologue cat-1 genes. These Amph-induced histone modifications are correlated with enhanced expression and function of CAT-2/TH and higher levels of dopamine, but decreased expression of CAT-1/VMAT in adult animals. Moreover, while adult animals pre-exposed to Amph do not show obvious behavioral defects, when challenged with Amph they exhibit Amph hypersensitivity, which is associated with a rapid increase in cat-2/TH mRNA. Because C. elegans has helped reveal neuronal and epigenetic mechanisms that are shared among animals as diverse as roundworms and humans, and because of the evolutionary conservation of the dopaminergic response to psychostimulants, data collected in this study could help us to identify the mechanisms through which Amph induces long-lasting physiological and behavioral changes in mammals.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Tyrosine 3-Monooxygenase
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins
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Embryonic Development
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Vesicular Monoamine Transport Proteins
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Amphetamine
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Type:
Article
Affiliation country:
United States