Seizures during pregnancy modify the development of hippocampal interneurons
of the offspring
Tiago Gurgel do Vale
a
, Alexandre Valotta da Silva
b
, Daiana Correia Lima
a
, Eliângela de Lima
a
,
Laila Brito Torres
a,c
, Ana Carolina Cossa
a
, Elaine Menezes de Oliveira
a
, Francisco Romero Cabral
d
,
Esper Abrão Cavalheiro
a
, Maria da Graça Naffah-Mazzacoratti
a,e
, Débora Amado
a,
⁎
a
Disciplina de Neurologia Experimental, Universidade Federal de São Paulo, São Paulo, Brasil
b
Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista, Mathias-Santos, Brasil
c
Instituto Evandro Chagas, Centro Nacional de Primatas PA, Ananindeua, Pará, Brasil
d
Instituto do Cérebro/Instituto de Ensino e Pesquisa Hospital Albert Einstein, São Paulo, Brasil
e
Departamento de Bioquímica, Universidade Federal de São Paulo, Campus São Paulo, São Paulo, Brasil
abstractarticle info
Article history:
Received 13 May 2010
Received in revised form 17 June 2010
Accepted 17 June 2010
Available online 14 August 2010
We investigated the effect of epileptic seizures during pregnancy on hippocampal expression of calcium-
binding proteins in the offspring. Female Wistar rats were submitted to the pilocarpine model and mated
during the chronic period. Seizure frequency was monitored over the entire pregnancy. Pups were perfused
at postnatal days 6 and 13, and the brains processed for Nissl staining and immunohistochemistry for NeuN,
calbindin, calretinin, and parvalbumin. Number of stained cells in the hippocampus was estimated through
stereological methods. Our results showed a decrease in epileptic seizure frequency during pregnancy. No
differences were observed in NeuN-positive, CR-positive cells, and Nissl-stained hippocampal neurons
between the groups. However, there was a significant decrease in calbindin-positive cells (P=0.005) and a
significant increase in parvalbumin-positive cells (P=0.02) in the experimental group when compared with
the control group. These results suggest that seizures during pregnancy affect the development of specific
hippocampal interneurons of the offspring.
© 2010 Elsevier Inc. All rights reserved.
1. Introduction
It is estimated that one in 200 (0.5%) pregnant women has epilepsy
[1]. Pregnant women with epilepsy are at increased risk for a variety
of maternal complications, as are the fetus and particularly the fetal
brain [2]. Pregnancy can change the course of epilepsy, altering seizure
frequency, for example. Furthermore, epilepsy and antiepileptic
drugs (AEDs) may have a significant impact on the course of pregnancy
and the fetus, particularly the developing fetal brain [1]. Currently
it is known that the relationships among maternal epilepsy, AED
metabolism, teratogenicity, and perinatal effects must be considered
simultaneously [3].
Children of mothers with epilepsy have lower perinatal vitality rates
(APGAR scores) and higher perinatal mortality rates then the general
population [4]. Moreover, children of mothers with epilepsy have lower
birth weight compared with controls [5–12]. Different authors have
observed a higher incidence of intrauterine growth retardation in
children of both mothers with epilepsy treated with AEDs and those
not treated, suggesting a possible direct effect of maternal epilepsy on
the fetus [10, 13]. Other studies have also reported low birth weight
and smaller head circumference in children of mothers with epilepsy,
particularly those on polytherapy and also depending on ethnic, genetic,
and environmental factors [4, 11]. Thus, there is a relationship between
maternal epilepsy and the development of the fetus; however, it has
not been established whether the epilepsy itself causes changes in
the fetus or the AEDs are responsible for such changes.
Generalized seizures can be extremely deleterious to the mother
and fetus as a result of the falls and anoxia to which both are exposed
[14]. Tonic–clonic generalized seizures may be particularly harmful
to the fetus, causing hypoxic injury of the central nervous system
and other organs. Moreover, these seizures lead to elevation of
maternal blood pressure and electrolytic changes, and may also result
in spontaneous abortion or intrauterine death [15]. However, it is
not known if seizures without fetal hypoxia cause damage [2]. Hallak
et al. [16] found that seizures in pregnant rats lead to changes in
hippocampal neurons, although the authors did not mention the type
and duration of seizures and the occurrence of hypoxia. It is unclear
whether other types of seizures, such as complex partial seizures and
absence seizures, have similar negative consequences [2].
Most clinical studies investigating the relationship between
epilepsy and pregnancy inevitably stumble on the interference by
Epilepsy & Behavior 19 (2010) 20–25
⁎ Corresponding author. Disciplina de Neurologia Experimental, Universidade
Federal de São Paulo, Rua Botucatu 862, 04023-900, São Paulo, SP Brasil.
E-mail address: amado.nexp@epm.br (D. Amado).
1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2010.06.032
Contents lists available at ScienceDirect
Epilepsy & Behavior
journal homepage: www.elsevier.com/locate/yebeh