Exploring the links between antiepileptic drugs and neurodevelopmental disorders or autism: the role of epigenetics

Autism spectrum disorders, also known as ASDs, appear in childhood and persist throughout life. Taking certain medications during pregnancy and daily exposure to risk factors such as teratogenic substances, like certain anti-epileptic drugs, leads to an increase in the number of cases of ASD. Anti-epileptic drugs are able to cross the placental barrier, so they can reach the embryo or fetus, causing developmental disorders and promoting the onset of ASD symptoms. 

In utero injection of antiepileptic drugs is one of the most widely used environmental animal models of ASD. Valproic acid (VPA) is an antiepileptic, and high doses of this drug are associated with a high teratogenic effect. It is therefore a risk factor for the development of ASDs. Prenatal exposure to topiramate, another antiepileptic, increases the risk of ASD and intellectual disability, in addition to the known risk of major malformations. Lamotrigine is an antiepileptic for which there is no known effect on neurodevelopment after prenatal exposure. However, lamotrigine may play an amplifying role when used in combination with another antiepileptic. 

My internship aims to identify specific DNA methylation changes in the blood and brain of mice after in utero exposure to valproic acid, topiramate or lamotrigine.  To this end, I will study epigenetics and more specifically DNA methylation. Environmental factors can affect gene expression by acting on DNA methylation. When these epigenetic variations occur during embryonic development, they may increase the risk of ASD induction. 

#Autism #Antiepileptic drugs #Epigenetic #Pyrosequencing #Animal study

Study of the genetic and epigenetic variability involved in the occurrence of Cannabic Hyperemesis Syndrome in chronic cannabis consumers

Cannabinoid hyperemesis syndrome (CHS) is a condition associated with chronic cannabis use, characterized by cyclic vomiting episodes often temporarily relieved by hot showers. It progresses through three phases: a prodromal phase with prolonged morning nausea without appetite loss, a hyperemetic phase marked by severe vomiting, abdominal pain, and sweating, and a recovery phase where symptoms resolve after cannabis cessation, the primary treatment.

The CANEMESE clinical study, conducted by the Poitiers University Hospital (CHU) under the coordination of Dr. Stéphanie PAIN, investigates the influence of cannabinoid concentrations and genetic variations (CYP2C9, CYP2C19, FAAH, TRPV1, CNR1, CNR2) on CHS development. The study compares two groups: « case » patients, chronic cannabis users who have developed CHS, and « control » patients, also chronic cannabis users (at least weekly) who have never experienced this syndrome.

The internship aims to expand genetic polymorphism analyses to new patients, mainly from Limoges and Poitiers, and potentially integrate an epigenetic dimension by studying DNA methylation in affected patients. These studies could help clarify the underlying mechanisms and improve CHS management. Techniques used to characterize these SNPs/variations include DNA extraction from blood samples, pyrosequencing, and the SNaPshot Multiplex method.

#Hyperemesis # DNA #Sequencing #Multiplex

internship supervisor

Claire-Lafay CHEBASSIER
& Stéphanie PAIN