Antiseizure medication in early nervous system development. Ion channels and synaptic proteins as principal targets

Abstract

The main strategy for the treatment of epilepsy is the use of pharmacological agents known as antiseizure medication (ASM). These drugs control the seizure onset and improves the life expectancy and quality of life of patients. Several ASMs are contraindicated during pregnancy, due to a potential teratogen risk. For this reason, the pharmacological treatments of the pregnant Women with Epilepsy (WWE) need comprehensive analyses to reduce fetal risk during the first trimester of pregnancy. The mechanisms by which ASM are teratogens are still under study and scientists in the field, propose different hypotheses. One of them, which will be addressed in this review, corresponds to the potential alteration of ASM on ion channels and proteins involved in relevant signaling and cellular responses (i.e., migration, differentiation) during embryonic development. The actual information related to the action of ASM and its possible targets it is poorly understood. In this review, we will focus on describing the eventual presence of some ion channels and synaptic proteins of the neurotransmitter signaling pathways present during early neural development, which could potentially interacting as targets of ASM. This information leads to elucidate whether these drugs would have the ability to affect critical signaling during periods of neural development that in turn could explain the fetal malformations observed by the use of ASM during pregnancy.

Mechanism of Robo1 in the pentylenetetrazol‐kindled epilepsy mouse model

“…An epileptic seizure is defined as a sudden occurrence of transient signs and symptoms caused by abnormal and excessive or synchronous neuronal activities in the brain 20 . Its etiology and pathogenesis are complex, involving ion channels, synapse‐associated proteins, genes, and other factors 21–23 . The most important pathological changes are synaptic remodeling of neurons and the formation of afferent excitatory loops in the hippocampus.…”

“… 20 Its etiology and pathogenesis are complex, involving ion channels, synapse‐associated proteins, genes, and other factors. 21 , 22 , 23 The most important pathological changes are synaptic remodeling of neurons and the formation of afferent excitatory loops in the hippocampus. Dendritic spines are an important component in the formation of synapses between neurons.…”

Respiratory Dysfunction in Epileptic Encephalopathies: Insights and Challenges

“…Effective seizure control through AEDs is closely linked to better respiratory outcomes. Seizures, especially convulsive seizures, can directly exacerbate respiratory dysfunction, so controlling them can minimize the immediate risk [ 36 ]. The presence of comorbidities, such as cognitive impairment or cardiac abnormalities, can complicate the management of respiratory dysfunction and influence patient outcomes.…”

“…Advances in gene therapy hold promise for addressing the underlying genetic mutations that contribute to epilepsy and respiratory dysfunction. Tailored gene-editing techniques may provide a path to targeted treatments [ 36 ]. Ongoing research aims to identify pharmacological agents that can modulate the neural pathways and neurotransmitter systems involved in respiratory control.…”

“…Engaging patients and their families in research efforts is invaluable. Their experiences and insights can inform the development of patient-centered interventions and research priorities [ 36 ]. In conclusion, the long-term implications of respiratory dysfunction in epileptic encephalopathies are substantial, affecting the quality of life, cognitive and behavioral outcomes, and even mortality risk.…”