Prenatal stress and febrile seizures effects on the epigenetic mechanisms involved in cognitive function following treatment with Searsia chirindensis.
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Date
2016
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Abstract
Febrile seizures are of growing concern in the health fraternity within the African continent. These
seizures predominantly affect children between the ages of 3 months and 5 years of age. Stress during
pregnancy may influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis in the
developing foetus. This has a tendency to increase the brain’s vulnerability to a number of insults
including febrile seizures. Current treatment for febrile seizures often has undesirable side effects
hence the need to find more effective alternatives. Searsia chirindensis (Searsia) is commonly used to
treat conditions associated with the heart, rheumatism and brain abnormalities. The focus of this study
was to investigate whether exposure to prenatal stress and early life febrile seizures may affect the
expression of genes that play a role in neuronal plasticity. For this we looked at the expression of the
MeCP2 and REST genes in the hippocampus. Furthermore, we investigated whether neuronal
malformations and the resulting cognitive deficits associated with exposure to early life stress
influences the concentration of the neurotrophic factor, BDNF and whether further exposure to febrile
seizures exacerbates the stress effect. We also investigated whether treating febrile convulsions with
Searsia attenuates the negative effects caused by stress on febrile seizure development as well as any
cognitive effects that may be caused by the exposure to stress and febrile seizures. Fourteen day old
(PND 14) pups were divided into the following groups 1) Normally reared Sprague-Dawley offspring
injected with saline (NSS). (2) Prenatally stressed offspring injected with saline (SS). (3) Normally
reared offspring with febrile seizures (NSFS). (4) Prenatally stressed offspring with febrile seizures
(SFS). (5) Normally reared offspring treated with Searsia (NS-S). (6) Prenatally stressed offspring
treated with Searsia (S-S). (7) Normally reared offspring with febrile seizures and treated with
Searsia (NSFS-S). (8) Prenatally stressed offspring with febrile seizures and treated with Searsia
(SFS-S). Lipopolysaccharide and kainic acid were used to induce the febrile seizures. The Morris
water maze (MWM) was used to assess learning and memory function and the elevated plus maze
(EPM) was used to assess anxiety-like behaviour in these young rats. MeCP2/REST genes expression
and the concentration of BDNF as well as AChE were quantified using an immunoassay on
hippocampal tissue. Our results showed that exposure to prenatal stress (SS) and febrile seizures
(NSFS) may impair cognitive behavioural function in the short-term. However, in the NSFS animals,
there seems to be an attempt to counteract the effects of febrile seizures with time. Furthermore,
exposure to prenatal stress impeded the release of the neurotrophic factor, BDNF, while attenuating
REST gene expression in febrile seizure animals. These factors may contribute to the hindering of
neurogenic properties in the young, thus leading to neuronal plasticity deficits and possibly cognitive
malfunction in later life. Treatment with Searsia attenuated the transient cognitive impairments
present following a seizure by influencing the concentration of hippocampal acetylcholine and
activating MeCP2 gene expression. This suggests a role for Searsia in the management of febrile
seizures and in attenuating the development of chronic cognitive deficits.
Description
Master of Medical Science in Human Physiology. University of KwaZulu-Natal, Westville 2016.
Keywords
Febrile convulsions., Pregnancy--Complications., Stress (Psychology)--Health aspects., Theses--Human physiology., Searsia chirindensis., Febrile seizures.