Oral glutamine supplementation increases seizure severity in a rodent model of mesial temporal lobe epilepsy.

Background: Glutamine synthetase (GS) is the only enzyme known to synthesize significant amounts of glutamine in mammals, and loss of GS in the hippocampus has been implicated in the pathophysiology of medication refractory mesial temporal lobe epilepsy (MTLE). Moreover, loss-of-function mutations of the GS gene causes severe epileptic encephalopathy, and supplementation with glutamine has been shown to normalize EEG and possibly improve the outcome in these patients. Here we examined whether oral glutamine supplementation is an effective treatment for MTLE by assessing the frequency and severity of seizures after supplementation in a translationally relevant model of the disease.Methods: Male Sprague Dawley rats (380-400 g) were allowed to drink unlimited amounts of glutamine in water (3.6% w/v; n = 8) or pure water (n = 8) for several weeks. Ten days after the start of glutamine supplementation, GS was chronically inhibited in the hippocampus to induce MTLE. Continuous video-intracranial EEG was collected for 21 days to determine the frequency and severity of seizures.Results: While there was no change in seizure frequency between the groups, the proportion of convulsive seizures was significantly higher in glutamine treated animals during the first three days of GS inhibition.Conclusion: The results suggest that oral glutamine supplementation transiently increases seizure severity in the initial stages of an epilepsy model, indicating a potential role of the amino acid in seizure propagation and epileptogenesis.

Attention to novelty in behaviorally inhibited adolescents moderates risk for anxiety.

BACKGROUND: Individual differences in specific components of attention contribute to behavioral reactivity and regulation. Children with the temperament of behavioral inhibition (BI) provide a good context for considering the manner in which certain components of attention shape behavior. Infants and children characterized as behaviorally inhibited manifest signs of heightened orienting to novelty. The current study considers whether this attention profile moderates risk for clinical anxiety disorders among adolescents with a history of BI. METHODS: Participants were assessed at multiple time points for BI, beginning in early childhood. At adolescence, event-related potentials (ERPs) were recorded during a three-stimulus auditory novelty oddball task, which employed frequent standard and infrequent deviant tones as well as a set of complex, novel sounds. Clinical diagnosis was carried out using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). P3 and mismatch negativity (MMN) components were examined at midline frontal, central, and parietal electrode sites. RESULTS: Individuals who displayed high levels of BI during childhood and increased P3 amplitude to novelty in adolescence were more likely to have a history of anxiety disorders compared to behaviorally inhibited adolescents with lower P3 amplitudes. Groups did not differ on measures of MMN. CONCLUSIONS: Increased neural responses to novelty moderate risk for anxiety disorders amongst individuals with a history of BI.