Fundación Descubre
Fundación Descubre
A team of scientists from the city of Cordoba has studied the effect of testosterone on behavior of the worm Caenorhabditis elegans, with the aim to analyze at the molecular level the interaction between the male hormone and the nervous system.
Previous research established a correlation between development of autistic behavior traits and level of exposure to testosterone during prenatal development. The research study, entitled “Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits?” has been published in the journal Frontiers in Cellular Neuroscience.
A team of scientists from the city of Cordoba has studied the effect of testosterone on behavior of the worm Caenorhabditis elegans, with the aim to analyze the interaction between the male hormone and the nervous system at the molecular level. Previous research established a correlation between autistic behavior traits and level of exposure to testosterone during prenatal development. The research study, entitled “Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits?” has been published in the journal Frontiers in Cellular Neuroscience.
The research group Genetics and Behavioral Disorders from the Maimonides Institute for Biomedical Research (IMIBIC) and the University of Cordoba has analyzed the effects of testosterone on the behavior of the nematode (“worm”) Caenorhabditis elegans. Previous research has established a direct correlation between exposure to high levels of testosterone during prenatal development and the risk of developing autistic behavior traits. People diagnosed with Autism Spectrum Disorders (ASD) have two types of well-defined symptoms: persistent deficits in social interaction and communication and restricted and repetitive patterns of behavior, activities or interests.
This research study, published in the journal Frontiers in Cellular Neuroscience as “Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen -dependent autistic traits?”, has provided two main results. Firstly, the research team has identified a C. elegans gene (named NHR -69), which acts as a testosterone receptor.
Secondly, they have shown that this male hormone produces effects in the nematode through epigenetic mechanisms, which do not affect the DNA sequence of genes but stably influence their expression. This means that environmental factors interact with the genome to induce stable changes in gene expression”, says to Fundación Descubre the Head of the team, Prof. Manuel Ruiz Rubio.
Tests with C. elegans
The IMIBIC research group has pioneered the use of Caenorhabditis elegans as an experimental system to analyze basic neurobiological mechanisms involved in autism in vivo. The main advantage of this worm is its simplicity: its body is about one millimeter, it has 302 neurons and 959 somatic cells. 'In addition, over 80 % of its proteins are homologous to human', says Professor Ruiz.
During the experiments, the team kept worms in the presence of testosterone in petri dishes, where the entire developmental process of nematode can take place. They analyzed two types of behaviour: mechanosensory response and involuntary pharyngeal pumping. In the former, the scientists “tapped” the worm with an eyebrow hair, 5 times at the forefront and 5 in the rear. During “normal” responses (in the absence of testosterone), worms move back when tapped in the forefront and forward when tapped in the rear in 100% of cases. By contrast, in individuals which were grown in the presence of the male hormone, this response was reduced by 20 to 30%, suggesting a dysfunction of the nervous system.
In the second test, researchers analyzed an involuntary behavioural trait: pharyngeal pumping, which occurs continuously and enables food intake. 'It would be equivalent to the function of our heart', explains Prof. Ruiz. In the absence of testosterone, almost 300 pulses take place per minute but in the presence of the hormone, the number of pulses decreases to about 250.
How does testosterone work?
This research has enabled establishment of a simple experimental model to study the effects of testosterone on the nervous system. In humans, the male hormone is known to interact with the androgen receptor (a protein) in the cell and then enters the cell nucleus, altering gene expression. Based on this evidence, the IMIBIC researchers searched the worm genome with the aim to identify genes homologous to the human androgen receptor.
By using C. elegans mutants (“worms” that lack a functional version of these genes), they found that NHR-69 gene was essential for the behavioral effect induced by testosterone. Thus, this gene likely encodes a receptor capable of interacting with testosterone in the nematode. Further reserach will help to provide a deeper understanding of the role of the NHR-69 gene in behavioural changes and to draw parallelisms with similar mechanisms of action in the human genome.
Another important conclusion from this study is that testosterone acts by an epigenetic mechanism, i.e. it causes stable changes in gene expression. To prove this, researchers exposed a generation of C.elegans individuals to testosterone. By contrast, the progeny of this generation was grown in testosterone-free medium. It was observed that the behavior of the second generation worms remained altered. This was true up to the fourth generation of worms. This result is interesting because it gives a hint of the molecular mechanisms of action of the hormone. In humans, there is also evidence that testosterone may be related to epigenetic mechanisms.
About autism
According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders (DSM -5) of the American Psychiatric Association, autism is defined as a disorder characterized by two types of symptoms: persistent deficits in social interaction and communication and restricted and repetitive patterns of behavior, interests or activities .
Nevertheless, people with ASD have other symptoms that are not the same in all cases or differ in intensity. There is also great variability in IQ and language abilities.
With regards to ASD causes, although studies with monozygotic twins suggest that they are predominantly genetic, environmental as well as epigenetic factors may also be involved. 'Understanding at the molecular level the causes and mechanisms underlying these disorders is essential to find the right therapies', explains Prof. Ruiz.
Reference:
Gámez-Del-Estal MM, Contreras I, Prieto-Pérez R, Ruiz-Rubio M. Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits? Frontiers in Cellular Neuroscience 2014 Mar 4;8:69. doi: 10.3389/fncel.2014.00069.
The research group Genetics and Behavioral Disorders from the Maimonides Institute for Biomedical Research (IMIBIC) and the University of Cordoba has analyzed the effects of testosterone on behavior of the nematode (“worm”) Caenorhabditis elegans. Previous research established a direct correlation between exposure to high levels of testosterone during prenatal development and risk of developing autistic behavior traits. People diagnosed with Autism Spectrum Disorders (ASD) have two types of well-defined symptoms: persistent deficits in social interaction and communication and restricted and repetitive patterns of behavior, activities or interests.
There are two main results from this study, published in the journal Frontiers in Cellular Neuroscience as “Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen -dependent autistic traits?”. Firstly, the research team has identified a C. elegans gene (named NHR -69), which acts as a testosterone receptor. Secondly, they have shown that this male hormone produces effects in the nematode through epigenetic mechanisms, which do not affect the DNA sequence of genes but stably influence their expression. This means that environmental factors interact with the genome to induce stable changes in gene expression”, says to Fundación Descubre Prof. Manuel Ruiz Rubio, head of the team.
Tests with C. elegans.
The IMIBIC research group has pioneered the use of Caenorhabditis elegans as an experimental system to analyze basic neurobiological mechanisms involved in autism in vivo. The main advantage of this worm is its simplicity: its body is about one millimeter, it has 302 neurons and 959 somatic cells. 'In addition, over 80 % of its proteins are homologous to human', says Professor Ruiz.
During experiments, the team kept worms in the presence of testosterone in petri dishes, where the entire developmental process of nematode takes place. They analyzed two types of behaviour: mechanosensory response and involuntary pharyngeal pumping. In the former, scientists “tapped” the worm with an eyebrow hair, 5 times at the forefront and 5 in the rear. During “normal” responses (in the absence of testosterone), worms move back when tapped in the forefront and forward when tapped in the rear in 100% of cases. By contrast, in individuals which were grown in the presence of the male hormone, this response was reduced by 20 to 30%, suggesting a dysfunction of the nervous system.
In the second test, researchers analyzed an involuntary behavioural trait: pharyngeal pumping, which occurs continuously and enables food intake. 'It would be equivalent to the function of our heart', explains Prof. Ruiz. In the absence of testosterone, almost 300 pulses take place per minute but in the presence of the hormone, the number of pulses decreases to about 250.
How does testosterone work?
This research has enabled establishment of a simple experimental model to study the effects of testosterone on the nervous system. In humans, the male hormone is known to interact with the androgen receptor (a protein) in the cell and then enters the cell nucleus, altering gene expression. Based on this evidence, IMIBIC researchers searched the worm genome with the aim to identify genes homologous to the human androgen receptor.
By using C. elegans mutants (“worms” that lack a functional version of these genes), they found that NHR-69 gene was essential for the behavioral effect induced by testosterone. Thus, this gene likely encodes a receptor capable of interacting with testosterone in the nematode. Further reserach will help to provide a deeper understanding of the role of the NHR-69 gene in behavioural changes and to draw parallelisms with similar mechanisms of action in the human genome.Another important conclusion from this study is that testosterone acts by an epigenetic mechanism, i.e. it causes stable changes in gene expression. To prove this, researchers exposed a generation of C.elegans individuals to testosterone. By contrast, the progeny of this generation was grown in testosterone-free medium. It was observed that the behavior of the second generation worms remained altered. This was true up to the fourth generation of worms. This result is interesting because it gives a hint of the molecular mechanisms of action of the hormone. In humans, there is also evidence that testosterone may be related to epigenetic mechanisms.About autismAccording to the latest version of the Diagnostic and Statistical Manual of Mental Disorders (DSM -5) of the American Psychiatric Association, autism is defined as a disorder characterized by two types of symptoms: persistent deficits in social interaction and communication and restricted and repetitive patterns of behavior, interests or activities .
Nevertheless, people with ASD have other symptoms that are not the same in all cases or differ in intensity. There is also great variability in IQ and language abilities. With regards to ASD causes, although studies with monozygotic twins suggest that they are predominantly genetic, environmental as well as epigenetic factors may also be involved. 'Understanding at the molecular level the causes and mechanisms underlying these disorders is essential to find the right therapies', explains Prof. Ruiz.
Reference:
Gámez-Del-Estal MM, Contreras I, Prieto-Pérez R, Ruiz-Rubio M. Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits? Frontiers in Cellular Neuroscience 2014 Mar 4;8:69. doi: 10.3389/fncel.2014.00069.
