Abstract
BackgroundStatus epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown.MethodsIn the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests.ResultsWe found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group.ConclusionsThese results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients.
Highlights
Status epilepticus (SE) is a life-threatening neurological disorder
Saracatinib reduces the frequency of epileptic spikes after SE Saracatinib, as a pharmacological inhibitor of the Fyn, is effective at suppressing epileptiform spikes [18]
We examined the effects of saracatinib on the frequency of spikes using our pilocarpine induced SE model
Summary
Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. A member of the Src family of kinases, is a tyrosine kinase without a receptor. It is widely involved in many physiological processes in the nervous system, including synaptic transmission, synaptic plasticity, oligodendrocyte differentiation, and dendritic spine development [5,6,7,8]. It plays critical roles in memory formation and cognitive function regulation by regulating hippocampal dendritic spine development in Alzheimer’s disease (AD) patients [7]. Aberrant Fyn activity leaded to speed up neurodegeneration in AD patients, and deficiency of Fyn or inhibiting its activity has been shown to restore
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