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Platelet GABA-transaminase in epileptic children: influence of epilepsy and anticonvulsants
R Arteaga1, J L Herranz, J A Armijo
1Neuropediatrics Service, M. de Valdecilla Hospital, Faculty of Medicine, University of Cantabria, Santander, Spain.
Insights
Platelet GABA-transaminase (GABA-T) activity is altered in epileptic children, with lower levels in untreated patients and elevated levels in those on anticonvulsants, particularly valproate. This suggests platelet GABA-T may serve as a marker for epilepsy and drug effects.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Epilepsy is a neurological disorder characterized by recurrent seizures.
- GABA-transaminase (GABA-T) is an enzyme involved in the metabolism of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter.
- Alterations in GABAergic neurotransmission are implicated in epilepsy and may be influenced by antiepileptic drugs.
Purpose of the Study:
- To investigate the relationship between platelet GABA-T activity and epilepsy in children.
- To compare GABA-T activity in newly diagnosed untreated epileptic children, chronically treated epileptic children, and healthy controls.
- To assess the impact of different antiepileptic drugs, specifically valproate, on platelet GABA-T activity.
Main Methods:
- Enzyme activity assay of platelet GABA-T was performed.
- 281 epileptic children (55 untreated, 226 treated) and 48 control children were studied.
- Statistical analysis was used to compare GABA-T activity between groups and correlate with seizure types and treatments.
Main Results:
- Untreated epileptic children exhibited lower platelet GABA-T activity compared to controls (P < 0.05).
- Treated epileptic children showed higher GABA-T activity than untreated children (P < 0.01).
- Valproate monotherapy significantly increased GABA-T activity compared to controls and untreated patients (P < 0.001). Patients on valproate had higher activity than those on other anticonvulsants (P < 0.001).
Conclusions:
- Platelet GABA-T activity is significantly altered in epileptic children, reflecting both the disease state and the effects of antiepileptic drug treatment.
- Valproate demonstrates a notable impact on increasing platelet GABA-T activity.
- Platelet GABA-T may serve as a useful peripheral biomarker for assessing GABAergic alterations and the pharmacodynamic effects of antiepileptic drugs in epilepsy.
Abstract:
The relationship between platelet GABA-transaminase (GABA-T) activity and either epilepsy or its treatment has been studied in 281 epileptic children: 55 were newly diagnosed untreated patients and 226 were chronically receiving anticonvulsants (154 in monotherapy and 72 in polytherapy). Results were compared with those from 48 control children. Untreated children had a GABA-T activity of 9.1 +/- 3.7 pmol/min/mg protein, lower than the control group (10.6 +/- 3.8 pmol/min/mg, P < 0.05), whereas treated epileptic children had higher values (11.9 +/- 6.3 pmol/min/mg) than those untreated (P < 0.01). In untreated children, the seven with absences and the nine with simple partial seizures had a GABA-T activity of 6.9 +/- 3.3 and 7.8 +/- 3.2 pmol/min/mg, respectively, lower than the control group (P < 0.05). In treated patients, those receiving valproate (VPA) in monotherapy had a GABA-T activity of 15.3 +/- 7.5 pmol/min/mg, higher than both the control group and the untreated children (P < 0.001). All patients receiving VPA in mono- or polytherapy had a higher activity than those receiving other anticonvulsants (16.4 +/- 8.4 vs. 9.9 +/- 3.9 pmol/min/mg, P < 0.001), the activity in Lennox syndrome and myoclonic epilepsies being significantly higher than in those with absences and partial epilepsy. GABA-T activity did not correlate with doses or trough steady-state serum levels of VPA. Platelet GABA-T could be useful as a peripheral marker of GABAergic alterations and GABAergic effects of antiepileptic drugs in epileptic patients.