Enhanced Aspartate Release Related to Epilepsy in (EL) Mice

Abstract

Previous studies have shown that potassium‐evoked, calcium‐dependent, endogenous aspartate release is greater from hippocampal slices of adult epileptic (EL) mice than from nonepileptic control C57BL/6J (B6) mice. To examine further the association between epilepsy and enhanced aspartate release in EL mice, endogenous neurotransmitter release from hippocampal slices was studied in young, seizure‐free EL mice and in two nonseizure control mouse strains, DDY and B6. DDY is the parental strain from which EL arose, and it has a genetic background similar to EL. Released amino acid neurotransmitters were quantitated by HPLC with fluorescent detection and were expressed as picomoles of amino acid released per minute of incubation per slice ± SEM. Aspartate release was significantly higher in EL mice (15.8 ± 0.8) than in either the control B6 or DDY mice (8.5 ± 1.4 and 8.4 ± 1.7, respectively). No significant differences were found among the B6, DDY, and EL mice for the release of glutamate (23.0 ± 2.0, 32.3 ± 5.8, and 25.9 ± 2.6, respectively) or GABA (23.5 ± 0.7, 19.5 ± 3.2, and 21.8 ± 3.2, respectively). Thus, enhanced aspartate release precedes the onset of EL seizures and may be related to the cause rather than to the effects of seizure activity.

Alteration of Brain Levels of Neurotransmitters and Amino Acids in Male F344 Rats Induced by Three-week Repeated Inhalation Exposure to 1-Bromopropane

“…Because ammonia is toxic to the nervous system, glutamine may have increased as a result of detoxification in the brain after chemical exposure. Aspartate is known as one of excitatory neurotransmitters 28,29) , an increase in locomotor activity was observed in rats exposed to 1BP 12) . Such behavioral changes may be related to the increase in cerebral aspartate observed in this study.…”

Reduction of glial glutamate transporters in the parietal cortex and hippocampus of the EL mouse

“…Although release of aspartate has been reported to be significantly higher in cortical slices from EL(+) mice than those from EL(–) (Higashihara et al . 1990), no difference in glutamate release between EL mice and DDY controls has been observed (Flavin and Seyfried 1994). It may be postulated, however, that a generalized increase in tissue glutamate may be involved in seizure activity, and that if excitatory neurons are more active, they may contain higher concentrations of glutamate.…”

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies

“…Ketone‐induced alterations in TCA cycle metabolites (oxaloacetate, citrate, succinyl‐CoA and α‐ketoglutarate) will favor the formation of glutamate over aspartate and thereby reduce brain aspartate, an excitatory neurotransmitter implicated in epilepsy (Flavin et al . 1991; Flavin and Seyfried 1994; Veech et al . 2001; Yudkoff et al .…”

“…Ketones stimulate glutamic acid decarboxylase activity that can potentially elevate GABA content in synaptosomes (Erecinska et al 1996;Daikhin and Yudkoff 1998;Yudkoff et al 2001). Ketone-induced alterations in TCA cycle metabolites (oxaloacetate, citrate, succinyl-CoA and a-ketoglutarate) will favor the formation of glutamate over aspartate and thereby reduce brain aspartate, an excitatory neurotransmitter implicated in epilepsy (Flavin et al 1991;Flavin and Seyfried 1994;Veech et al 2001;Yudkoff et al 2001). Reductions in excitatory neurotransmitters (glutamate and aspartate) together with elevations in GABA could decrease neuronal excitation and increase inhibition.…”