Summary: A new study used C. elegans to investigate the long-term effects of amphetamine exposure during embryogenesis, revealing significant alterations in dopamine-related genes and proteins. These changes lead to increased sensitivity to amphetamines in adulthood, highlighting the potential risks to humans.
The study highlights the need to carefully consider amphetamine use during pregnancy due to its lasting impact on brain function.
Highlights:
- Genetic alteration: Exposure to high doses of amphetamine alters the expression of dopamine-related genes.
- Behavioral impact: Exposed embryos show increased sensitivity to amphetamines in adulthood.
- Epigenetic mechanisms: The results suggest epigenetic changes resulting from embryonic exposure.
Source: FAU
Amphetamine is a psychostimulant used to treat various brain dysfunctions. However, it is a widely abused drug. In fact, amphetamine and amphetamine-derived compounds, such as methamphetamine (Meth), are among the most widely abused psychostimulants in the world.
The neurological effects caused by acute or chronic amphetamine use have been widely studied and several studies have shown that proteins involved in the synthesis, storage, release and reuptake of dopamine (DA), a neurotransmitter that plays a role as in the “reward” center, are either direct targets or indirectly affected by these drugs.
During pregnancy, the effects of therapeutic doses of amphetamine have been studied on birth outcomes in humans. However, comprehensive investigation of the mechanisms underlying the long-term effects of embryonic exposure to addictive doses of amphetamine remains largely unexplored.
Using a small worm, C. elegans, Florida Atlantic University researchers are the first to study the underlying mechanisms within the embryo after exposure to high concentrations of amphetamines, discovering their long-lasting effects. term.
For the study, researchers examined whether exposure to high doses of amphetamine throughout embryogenesis led to changes in the expression and function of two major dopamine proteins, tyrosine hydroxylase (TH) and the vesicular monoamine transporter (VMAT). Both TH and VMAT play an important role in the synthesis, storage and release of dopamine – essential for various brain functions and behaviors.
The results of the study, published in the International Journal of Molecular Sciences, show that following exposure to high doses of amphetamine during embryogenesis, the expression of specific genes of the dopaminergic system (dopamine transporter, TH and VMAT) is altered in adult C. elegans via mechanisms epigenetics.
These changes in gene and, therefore, protein expression cause behavioral changes in adult animals, such that animals given amphetamine during embryogenesis were more susceptible to drug-induced behaviors. ‘amphetamine.
“The dopamine response to amphetamines and the mechanisms underlying histone methylation are highly conserved across diverse species, so we used C. elegans to examine the long-term effects caused by embryonic exposure to amphetamines” , said Lucia Carvelli, Ph.D., lead author and associate professor of neuroscience, FAU Harriet L. Wilkes Honors College and member of the FAU Stiles-Nicholson Brain Institute.
“It is important to note that although we used C. elegans as a model system, our goal is to understand how amphetamine acts in humans.”
One advantage of the model used by the researchers is that C. elegans embryos can develop outside the uterus and in the absence of maternal care.
“Our results were not influenced by possible epigenetic or behavioral modifications induced by amphetamines and transmitted through maternal care, but they are a direct consequence of biological alterations in the embryo,” Carvelli said.
Behavioral research data shows that, following embryonic exposure to amphetamine, adult animals exhibit an increased response to amphetamines. This suggests that altered expression of TH and VMAT caused by continuous exposure to amphetamines during embryogenesis generates animals hypersensitive to amphetamines.
“Given that our results are in agreement with data showing that mice overexpressing TH exhibit enhanced amphetamine-induced behaviors and that rats chronically treated with amphetamine exhibit a lasting increase in striatal dopamine reuptake , our results establish C. elegans as an effective and inexpensive model for studying long-lasting physiological changes caused by prenatal amphetamine exposure,” Carvelli said.
Co-authors of the study are Tao Ke, Ph.D., a postdoctoral researcher in the Carvelli lab; Kate E. Poquette, FAU undergraduate student; and Sophia L. Amro Gazze, a student at FAU High School.
Funding: This research was supported by the National Institute on Drug Abuse, National Institutes of Health (grant no. DA042156), awarded to Carvelli.
About this neurodevelopment research news
Author: Gisèle Galoustien
Source: FAU
Contact: Gisèle Galoustien – FAU
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Amphetamine exposure during embryogenesis alters the expression and function of tyrosine hydroxylase and vesicular monoamine transporter in adult C. elegans” by Lucia Carvelli et al. International Journal of Molecular Sciences
Abstract
Amphetamine exposure during embryogenesis alters the expression and function of tyrosine hydroxylase and vesicular monoamine transporter in adult C. elegans
Amphetamines (Amph) are psychostimulants widely used as physical and cognitive stimulants. However, the long-term effects of prenatal exposure to Amph have been poorly studied.
Here we show that continued exposure to Amph during early development induces lasting changes in histone methylation at C. elegans tyrosine hydroxylase (TH) homolog cat-2 and the vesicular monoamine transporter (VMAT) homolog cat-1 Genoa.
These Amph-induced histone modifications correlate with enhanced CAT-2/TH expression and function and higher dopamine levels, but with decreased CAT-1/VMAT expression in animals adults.
Furthermore, although adult animals preexposed to Amph do not exhibit obvious behavioral defects, when challenged with Amph, they exhibit hypersensitivity to Amph, which is associated with a rapid increase in cat-2/TH mRNA.
Because C. elegans has helped reveal shared neural and epigenetic mechanisms in animals as diverse as roundworms and humans, and because of the evolutionary conservation of the dopaminergic response to psychostimulants, the data collected in this study could help us identify the mechanisms by which Amph induces long-term effects. lasting physiological and behavioral changes in mammals.