Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant
Aleksey V Zaitsev1, Sergey L Malkin1, Tatyana Y Postnikova1
1Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia.
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.
Insights
Ceftriaxone (CTX) treatment in rats showed increased excitatory amino acid transporter 2 (EAAT2) mRNA but not protein, resulting in only mild anticonvulsant effects against seizures. This suggests limited potential for CTX in treating pharmacoresistant epilepsy.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Epilepsy affects millions, with 20-30% of patients unresponsive to current antiepileptic drugs.
- Modulating glutamate uptake via excitatory amino acid transporter 2 (EAAT2) is a potential strategy for pharmacoresistant epilepsy.
- Previous studies on ceftriaxone (CTX) show conflicting results regarding its anticonvulsant effects and impact on EAAT2.
Purpose of the Study:
- To investigate the effects of CTX on EAAT2 expression, glutamatergic neurotransmission, and anticonvulsant action in young rats.
- To clarify the discrepancy in previous research regarding CTX's efficacy.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) and Western blot analysis to assess EAAT2 mRNA and protein levels in the hippocampus.
- Maximal electroshock threshold test (MEST) to evaluate anticonvulsant effects against pentylenetetrazol (PTZ)-induced seizures.
- Electrophysiological recordings to assess glutamatergic neurotransmission in the hippocampus and temporal cortex.
Main Results:
- CTX treatment increased EAAT2 mRNA but not protein levels in the rat hippocampus.
- CTX exhibited only a mild anticonvulsant effect on PTZ-induced convulsions.
- Glutamatergic neurotransmission was largely unaffected, though field excitatory postsynaptic potential (fEPSP) amplitudes decreased with intense stimulation.
Conclusions:
- CTX treatment in young rats does not lead to significant EAAT2 overexpression, explaining its weak antiseizure effect.
- The findings provide insights into the limited impact of EAAT2 modulation by CTX on brain function and epilepsy treatment.
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