Neuronal deficits in mice following phenobarbital exposure during various periods in fetal development

Bergman, Arieh; Roselli-Austin, L; Yedwab, Gideon; Yanai, Joseph

doi:10.1159/000145319

Cited by 25 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Related to effects on brain development, exposure to phenobarbital during gestation led to a significant decrease in cell proliferation in an area of the hypothalamus (the medial preoptic area) of female Sabra mice [169], decreased number of hippocampal pyramidal cells [170–173], and decreased number of cerebellar Purkinje and granule cells [174]. In light of data showing a similar effect after phenytoin, it has been suggested that early life exposure to AEDs can cause increased programmed cell death, a potentially devastating effect for the developing brain (discussed further below).…”

Section: Animal (Rodent) In Utero Aed Exposurementioning

confidence: 99%

Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research

Bath

Scharfman

2013

Epilepsy & Behavior

View full text Add to dashboard Cite

Epilepsy affects approximately 1% of children under the age of 15, making it a very common neurological disorder in the pediatric population (Russ et al., 2012 [1]). In addition, ∼0.4–0.8% of all pregnant women have some form of epilepsy (Hauser et al., 1996a,b; Borthen et al., 2009; Krishnamurthy, 2012 [2–5]). Despite the potential deleterious effects of antiepileptic drugs (AEDs) on the developing brain, their use is still required for seizure control in pregnant women (Krishnamurthy, 2012 [5]), and they represent the standard approach for treating children with epilepsy (Chu-Shore and Thiele, 2010; Quach et al., 2010; Verrotti et al., 2011 [6–8]). Even when AEDs are effective, there are potential side effects, including cognitive and affective changes or altered sleep and appetite. The consequences of AED exposure in development have been studied extensively (Canger et al., 1999; Modi et al., 2011a,b; Oguni, 2011 [9–12]). Despite intensive study, there is still debate about the long-term consequences of early life AED exposure. Here, we consider the evidence to date that AED exposure, either prenatally or in early postnatal life, has significant adverse effects on the developing brain and incorporate studies of laboratory animals as well as those of patients. We also note the areas of research where greater clarity seems critical in order to make significant advances. A greater understanding of the impact of AEDs on somatic, cognitive and behavioral development has substantial value because it has the potential to inform clinical practice and guide studies aimed at understanding the genetic and molecular bases of comorbid pathologies associated with common treatment regimens. Understanding these effects has the potential to lead to AEDs with fewer side effects. Such advances would expand treatment options, diminish the risk associated with AED exposure in susceptible populations, and improve the quality of life and health outcomes of children with epilepsy and children born to women who took AEDs during pregnancy.

show abstract

Section: Animal (Rodent) In Utero Aed Exposurementioning

confidence: 99%

Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research

Bath

Scharfman

2013

Epilepsy & Behavior

View full text Add to dashboard Cite

show abstract

“…Indeed, prenatal PhB treatment, which affected the MPOA in the present studies, also affected sex hormones and reproductive functions [Gupta et al, 1980a, b]. Prenatal and neonatal exposure to PhB affected neuronal number and various regions of the brain Bergman et al, 1980;. The surviving cells exhibited changes in the dendritic spines [Yanai and Iser, 1981] as well as ultrastructural changes [Fishman et al, 1981].…”

Section: Discussionmentioning

confidence: 79%

“…The sexual function was also impaired in both sexes. It is known that the hypothalamus develops prenatally in the rodent [Crep, 1974;Ifft, 1972;Shimada and Nakamura, 1973] and that administration of PhB to pregnant ani mals caused long-lasting neuronal deficits in prenatally forming neurons in the cerebel lum and hippocampus [Bergman et al, 1980;Yanai et al, 1979]. The present experiment was designed to investigate in mice whether neuronal number and rate of proliferation of the MPOA cells are sexually dimorphic in the MPOA, and to study the effect of PhB, administered prenatally on these parameters.…”

Section: Introductionmentioning

confidence: 99%

Morphological Alterations in the Medial Preoptic Area After Prenatal Administration of Phenobarbital

Yanai¹,

Woolf²,

Feigenbaum³

1982

Cells Tissues Organs

Self Cite

View full text Add to dashboard Cite

Pregnant Sabra mice received 3 g phenobarbital per kilogram milled food from gestational days (GD) 9 to 18 as their only food source; control females received milled food. All the females were divided into three groups and injected intraperitoneally with a single dose of ³H-thymidine on GD 13, 15 or 17. At 50 days of age the offspring were perfused with 10% neutral formalin and their brains removed and prepared for autoradiography. Matching sagittal sections of the offspring were selected for the study of the medial preoptic area (MPOA) of the hypothalamus. The total number of cells per section was not significantly different between males and females, however, there was a greater cellular packing density (cell/mm²) in females (p < 0.05). This sex difference disappeared in treated offspring, possibly due to a 76% decrease on GD 13 in the rate of cell proliferation in females (number of labeled cells but not in males (p < 0.001); the greatest decrease in the number of labeled cells occurred in the sexually dimorphic areas of the MPOA (p < 0.001). The area of the sagittal section of the MPOA did not differ significantly between sexes or treatments.

show abstract

“…Transgenic mice that express a stabilized form of β‐catenin in neuronal progenitor cells develop grossly enlarged brains with a concomitant increase in cerebral cortical surface (Chenn & Walsh, 2003). Treatment of rodents with phenobarbital revealed an interference with cellular proliferation, resulting in decreased brain weight and neuronal number (Yanai et al., 1979, 1981; Bergman et al., 1980).…”

Section: Main Events Of the Cns Development And Their Impairment By Aedsmentioning

confidence: 99%

Neurologic birth defects after prenatal exposure to antiepileptic drugs

Uziel

Rozental

2008

Epilepsia

View full text Add to dashboard Cite

SUMMARYMaternal epilepsy has a potential for fetal injury, either antiepileptic drug (AED)-induced or as a consequence of seizures per se. The intent of this article is to explore this relationship, discussing similar patterns of malformations seen with AEDs or different disease exposure during pregnancy, and the potential role of gap junctional intercellular communication in abnormal morphogenesis.

show abstract

Neuronal deficits in mice following phenobarbital exposure during various periods in fetal development

Cited by 25 publications

References 7 publications

Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research

Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research

Morphological Alterations in the Medial Preoptic Area After Prenatal Administration of Phenobarbital

Neurologic birth defects after prenatal exposure to antiepileptic drugs

Contact Info

Product

Resources

About