PMID- 31766528 OWN - NLM STAT- MEDLINE DCOM- 20200420 LR - 20200420 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 23 DP - 2019 Nov 21 TI - Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats. LID - 10.3390/ijms20235852 [doi] LID - 5852 AB - 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. FAU - Zaitsev, Aleksey V AU - Zaitsev AV AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Malkin, Sergey L AU - Malkin SL AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Postnikova, Tatyana Y AU - Postnikova TY AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Smolensky, Ilya V AU - Smolensky IV AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Zubareva, Olga E AU - Zubareva OE AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Romanova, Irina V AU - Romanova IV AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Zakharova, Maria V AU - Zakharova MV AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Karyakin, Vladimir B AU - Karyakin VB AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. FAU - Zavyalov, Vladimir AU - Zavyalov V AD - Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia. LA - eng GR - 17-04-00898/capital ER, Cyrillicsmall o, Cyrillicsmall es, Cyrillicsmall es, Cyrillicsmall i, Cyrillicsmall short i, Cyrillicsmall es, Cyrillicsmall ka, Cyrillicsmall i, Cyrillicsmall short i, Cyrillic capital EF, Cyrillicsmall o, Cyrillicsmall en, Cyrillicsmall de, Cyrillic capital EF, Cyrillicsmall u, Cyrillicsmall en, Cyrillicsmall de, Cyrillicsmall a, Cyrillicsmall em, Cyrillicsmall ie, Cyrillicsmall en, Cyrillicsmall te, Cyrillicsmall a, Cyrillicsmall el, Cyrillicsmall soft sign, Cyrillicsmall en, Cyrillicsmall yeru, Cyrillicsmall ha, Cyrillic capital I, Cyrillicsmall es, Cyrillicsmall es, Cyrillicsmall el, Cyrillicsmall ie, Cyrillicsmall de, Cyrillicsmall o, Cyrillicsmall ve, Cyrillicsmall a, Cyrillicsmall en, Cyrillicsmall i, Cyrillicsmall short i, Cyrillic (capital ER, Cyrilliccapital EF, Cyrilliccapital EF, Cyrilliccapital I, Cyrillic)/ GR - 17-00-00408/capital ER, Cyrillicsmall o, Cyrillicsmall es, Cyrillicsmall es, Cyrillicsmall i, Cyrillicsmall short i, Cyrillicsmall es, Cyrillicsmall ka, Cyrillicsmall i, Cyrillicsmall short i, Cyrillic capital EF, Cyrillicsmall o, Cyrillicsmall en, Cyrillicsmall de, Cyrillic capital EF, Cyrillicsmall u, Cyrillicsmall en, Cyrillicsmall de, Cyrillicsmall a, Cyrillicsmall em, Cyrillicsmall ie, Cyrillicsmall en, Cyrillicsmall te, Cyrillicsmall a, Cyrillicsmall el, Cyrillicsmall soft sign, Cyrillicsmall en, Cyrillicsmall yeru, Cyrillicsmall ha, Cyrillic capital I, Cyrillicsmall es, Cyrillicsmall es, Cyrillicsmall el, Cyrillicsmall ie, Cyrillicsmall de, Cyrillicsmall o, Cyrillicsmall ve, Cyrillicsmall a, Cyrillicsmall en, Cyrillicsmall i, Cyrillicsmall short i, Cyrillic (capital ER, Cyrilliccapital EF, Cyrilliccapital EF, Cyrilliccapital I, Cyrillic)/ GR - 0132-2018-0008/Program of the Presidium of the RAS/ PT - Journal Article DEP - 20191121 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anticonvulsants) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Slc1a2 protein, rat) RN - 3KX376GY7L (Glutamic Acid) RN - 75J73V1629 (Ceftriaxone) SB - IM MH - Animals MH - Anticonvulsants/pharmacology MH - Ceftriaxone/*pharmacology MH - Epilepsy/drug therapy/genetics/physiopathology MH - Excitatory Amino Acid Transporter 2/*genetics/metabolism MH - Excitatory Postsynaptic Potentials/drug effects/genetics/physiology MH - Gene Expression/*drug effects MH - Glutamic Acid/metabolism MH - Hippocampus/drug effects/metabolism/physiopathology MH - Male MH - Rats, Wistar MH - Seizures/*drug therapy/genetics/physiopathology MH - Synaptic Transmission/*drug effects/genetics/physiology MH - Temporal Lobe/drug effects/metabolism/physiopathology PMC - PMC6928884 OTO - NOTNLM OT - animal model OT - cephalosporin OT - epilepsy OT - excitatory amino acid transporter OT - hippocampus OT - maximal electroshock threshold OT - pentylenetetrazol OT - temporal cortex COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2019/11/27 06:00 MHDA- 2020/04/21 06:00 PMCR- 2019/12/01 CRDT- 2019/11/27 06:00 PHST- 2019/09/24 00:00 [received] PHST- 2019/11/13 00:00 [revised] PHST- 2019/11/20 00:00 [accepted] PHST- 2019/11/27 06:00 [entrez] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/04/21 06:00 [medline] PHST- 2019/12/01 00:00 [pmc-release] AID - ijms20235852 [pii] AID - ijms-20-05852 [pii] AID - 10.3390/ijms20235852 [doi] PST - epublish SO - Int J Mol Sci. 2019 Nov 21;20(23):5852. doi: 10.3390/ijms20235852.