An evaluation of a human stem cell line to identify risk of developmental neurotoxicity with antiepileptic drugs

Cao, William S.; Livesey, John C.; Halliwell, Robert F.

doi:10.1016/j.tiv.2015.01.010

Cited by 14 publications

(7 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The anticonvulsant drugs vigabatrin (200 mg/kg/day), valproate (100 mg/kg/day) and lamotrigine (20 mg/kg/day) can cause severe cortical malformations upon fetal exposure (Manent et al, 2007 , 2008 ) and fetal valproate exposure (600 mg/kg at E12.5) disturbs the formation of tonotopic maps (Dubiel and Kulesza, 2015 ), suggesting that these substances can in animal experiments impair neuronal migration and functional differentiation. Also in cultures of hNSCs chronic application of the anticonvulsant substances phentobarbital (10 μM), valproate (10 μM), lamotrigine (1 μM) or carmazepine (1 μM) reduces cell viability (Cao et al, 2015 ). In humans, fetal exposure to these drugs is known to trigger long-term structural, behavioral and cognitive defects including modification of the brain mass, learning and memory impairments, anxiety, social interaction and sensorimotor integration disabilities (for review Turski and Ikonomidou, 2012 ).…”

Section: Pathophysiological Implications Of Disturbed Perinatal Neuromentioning

confidence: 99%

Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology

Kirischuk

Sinning

Blanquie

et al. 2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Animal and human studies revealed that patterned neuronal activity is an inherent feature of developing nervous systems. This review summarizes our current knowledge about the mechanisms generating early electrical activity patterns and their impact on structural and functional development of the cerebral cortex. All neocortical areas display distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, intermittent spontaneous activity is synchronized within small neuronal networks, becoming more complex with further development. This transition is accompanied by a gradual shift from electrical to chemical synaptic transmission, with a particular role of non-synaptic tonic currents before the onset of phasic synaptic activity. In this review article we first describe functional impacts of classical neurotransmitters (GABA, glutamate) and modulatory systems (e.g., acetylcholine, ACh) on early neuronal activities in the neocortex with special emphasis on electrical synapses, nonsynaptic and synaptic currents. Early neuronal activity influences probably all developmental processes and is crucial for the proper formation of neuronal circuits. In the second part of our review, we illustrate how specific activity patterns might interfere with distinct neurodevelopmental processes like proliferation, migration, axonal and dendritic sprouting, synapse formation and neurotransmitter specification. Finally, we present evidence that transient alterations in neuronal activity during restricted perinatal periods can lead to persistent changes in functional connectivity and therefore might underlie the manifestation of neurological and neuropsychiatric diseases.

show abstract

Section: Pathophysiological Implications Of Disturbed Perinatal Neuromentioning

confidence: 99%

Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology

Kirischuk

Sinning

Blanquie

et al. 2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In the current study we used TERA2.cl.SP12, a single human pluripotent stem cell line, with a simple and robust protocol, to differentiate both neurons and glial cells and characterized their development and functional maturation over 1 year in culture. From immunolabeling, we determined that neurons began to appear within 2 weeks of the start of neural differentiation and continued to expand for at least 3 months, as previously reported (e.g., Coyne et al, 2011 ; Cao et al, 2015 ). Our immunoblotting of the neural protein, β-III tubulin expression showed strong expression from 2 months through to 12 months in culture, indicating stable and prolonged viability of neurons.…”

Section: Discussionmentioning

confidence: 71%

Neuropharmacology of human TERA2.cl.SP12 stem cell-derived neurons in ultra-long-term culture for antiseizure drug discovery

et al. 2023

Self Cite

View full text Add to dashboard Cite

Modeling the complex and prolonged development of the mammalian central nervous system in vitro remains a profound challenge. Most studies of human stem cell derived neurons are conducted over days to weeks and may or may not include glia. Here we have utilized a single human pluripotent stem cell line, TERA2.cl.SP12 to derive both neurons and glial cells and determined their differentiation and functional maturation over 1 year in culture together with their ability to display epileptiform activity in response to pro-convulsant agents and to detect antiseizure drug actions. Our experiments show that these human stem cells differentiate in vitro into mature neurons and glia cells and form inhibitory and excitatory synapses and integrated neural circuits over 6–8 months, paralleling early human neurogenesis in vivo; these neuroglia cultures display complex electrochemical signaling including high frequency trains of action potentials from single neurons, neural network bursts and highly synchronized, rhythmical firing patterns. Neural activity in our 2D neuron–glia circuits is modulated by a variety of voltage-gated and ligand-gated ion channel acting drugs and these actions were consistent in both young and highly mature neuron cultures. We also show for the first time that spontaneous and epileptiform activity is modulated by first, second and third generation antiseizure agents consistent with animal and human studies. Together, our observations strongly support the value of long-term human stem cell-derived neuroglial cultures in disease modeling and neuropsychiatric drug discovery.

show abstract

“…Also, exposure to 375 μM of CBZ decreased astrocyte and neuronal differentiation, which is confirmed by low expression levels of GFAP and βIII-tubulin proteins [ 41 ]. Cao et al also showed that treatment with 100 μM of CBZ disrupted neurogenesis in TERA2.cl.SP12 human stem cells [ 42 ].…”

Section: The First-generation Asm and Neurogenesismentioning

confidence: 99%

“…In an in vitro model of neurogenesis using human stem cells (TERA2.cl.SP12) which subsequently give rise to neurons, PB at 100–1000 μM alleviated the viability of stem cells [ 42 ]. Moreover, 10 days of treatment with a high concentration of PB (>1000 μM) markedly declined the viability, migration, astrocyte, or neuronal differentiations in isolated human NSC [ 41 ].…”

Section: The First-generation Asm and Neurogenesismentioning

confidence: 99%

Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals

Alavi,

Al-Asady,

Fanoudi

et al. 2024

Heliyon

View full text Add to dashboard Cite

An evaluation of a human stem cell line to identify risk of developmental neurotoxicity with antiepileptic drugs

Cited by 14 publications

References 44 publications

Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology

Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology

Neuropharmacology of human TERA2.cl.SP12 stem cell-derived neurons in ultra-long-term culture for antiseizure drug discovery

Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals

Contact Info

Product

Resources

About