Correlation of 3-mercaptopropionic acid induced seizures and changes in striatal neurotransmitters monitored by microdialysis

Abstract

Objectives The goal of this study was to use a status epilepticus steady-state chemical model in rats using the convulsant, 3-mercaptopropionic acid (3-MPA), and to compare the changes in striatal neurotransmission on a slow (5 minute) and fast (60 second) timescale. In vivo microdialysis was combined with electrophysiological methods in order to provide a complete evaluation of the dynamics of the results obtained. Objective To compare the effects of a steady-state chemical model pof status epilepticus on striatal amino-acid and amine neurotransmitters contents, as measured via in vivo microdialysis combined with electrophysiological methods. Measurements were performed on samples collected every 60 seconds and every 5 minutes. “Fast” (60s) and “slow” (5 min.) sampling timescales were selected, to gain more insight into the dynamics of GABA synthesis inhibition and of its effects on other neurotransmitters and on cortical electrical activity. Methods 3-MPA was administered in the form of an intra-venous load(60 mg/kg) followed by a constant infusion (50 mg/kg/min) for min. Microdialysis samples were collected from the striatum at intervals of 5 minutes and 60 seconds and analyzed for biogenic amine and amino acid neurotransmitters. ECoG activity was monitored via screws placed over the cortex. Results In the 5 minute samples, glutamate (Glu) increased and γ-aminobutyric acid (GABA) decreased monotonically while changes in dopamine (DA) concentration were bimodal. In the sixty second samples, Glu changes were bimodal, a feature that was not apparent with the five minute samples. ECoG activity was indicative of status epilepticus. Conclusions This study describes the combination of in vivo microdialysis with electrophysiology to monitor the effect of 3-MPA on neurotransmission in the brain. This led to a better understanding of the chemical changes in the striatum due to the applied 3-MPA chemical model of status epilepticus.

Characterization of Biosensors Based on Recombinant Glutamate Oxidase: Comparison of Crosslinking Agents in Terms of Enzyme Loading and Efficiency Parameters

“…The two main approaches to measuring long-term brain Glu levels in vivo are microdialysis [17,18] and electrochemical biosensors [13,19,20]. A temporal resolution of ~1 min has been achieved using microdialysis for the detection of neurotransmitters such as serotonin [21] and Glu [22]. In contrast, biosensors represent a more useful approach for monitoring fast concentration dynamics of Glu (sub-second scale) due to the higher spatial and temporal resolution achievable with implantable amperometric biosensors.…”

Design, synthesis, and evaluation of anticonvulsant activities of benzoxazole derivatives containing the 1,2,4‐triazolone moiety

“…3‐Mercaptopropionic acid (3‐MP), as a competitive inhibitor of glutamate decarboxylase, can inhibit the synthesis of GABA, subsequently decreasing the levels of this neurotransmitter in the brain . Bicuculline (BIC), a competitive GABA A receptor antagonist, is known to produce seizures in mice after subcutaneous injection at low dose .…”

Assessment of the developmental toxicity of nanoparticles in anex vivo3D model, the murine limb bud culture system

“…The maximum concentration of MPA on QD surfaces (for 100 nM QDs) corresponds to 68 mM MPA, not previously reported as toxic. MPA in high micromolar concentrations (4500 mM) can induce seizures in vivo (Crick et al, 2014). It is likely that the increased incidence in cleft palate observed after the administration of repeated high doses of MPA to mice were also due to maternal toxicity, manifested as mild seizures and a decrease in body weight gain (Ding et al, 2004).…”