Abstract
Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20–30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.
Highlights
In the present study, we investigated the effects of CTX treatment on the mRNA and protein expression level of EAATs in the temporal cortex and dorsal hippocampus using a real-time quantitative PCR assay and a Western blot analysis
We investigated the effects of CTX treatment (200 mg/kg, once per day) for 1, 3, and 7 days on the gene expression of two astrocytic transporters, Eaat1 and Eaat2, and a neuronal transporter, Eaat3, in the dorsal hippocampus and temporal cortex of 3-week-old male Wistar rats
As shown by the two-way analysis of variance (ANOVA), there was no significant difference in Eaat1 and Eaat2 mRNA production (Figure 1a,c)
Summary
According to a report by the World Health Organization, it affects about 50 million people worldwide [1]. Despite the availability of a wide range of antiepileptic drugs, these cannot prevent seizures in 20–30% of patients [2,3,4]. Because of the lack of therapeutic efficacy, it is crucial to develop new pharmacological strategies to control seizures. Glutamate accumulation in extracellular spaces has been observed in some pharmacoresistant forms of epilepsy [5,6,7,8]. Modulation of glutamate uptake may be a potential treatment for pharmacoresistant epilepsy [9]
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