Excitatory and Inhibitory Amino Acids in Cerebrospinal Fluid of Familial Spontaneous Epileptic Cats

Abstract Objective: To evaluate the excitatory and inhibitory amino acids in the cerebrospinal fluid (CSF) from cats with familial spontaneous epilepsy (FSEC). Animals: Thirteen epileptic cats (suspected homozygotes: Affected) and nine non-epileptic cats (suspected heterozygotes: Unaffected) from FSEC line, and six clinical healthy cats which were unrelated FSEC line (Healthy). Procedures: CSF samples were collected before and after vestibular stimulation, which induced generalized seizures only in the affected cats. Excitatory/inhibitory amino acids (aspartate, glutamate, serine, glycine taurine, and gamma-aminobutyric acid (GABA)) levels in the CSF were analyzed by high performance liquid chromatography. In addition, CSF samples from five Affected cats in the interictal phase, four Unaffected cats, and three Healthy cats were used for metabolomics. Results: There was no difference in CSF glutamate concentrations between Affected and Healthy groups, while significantly lower glutamate concentrations were detected in the unaffected group. Following vestibular stimulation, glutamate concentrations were significantly elevated in the Unaffected and Healthy groups, but not in the Affected group. Moreover, the affected group exhibited the lower glutamine concentrations than the Healthy group. There was no difference in GABA concentrations between the groups, although some Affected cats showed elevated GABA. Conclusions and clinical relevance: In FSEC, an imbalance between excitatory and inhibitory neurotransmitters may not be the direct cause of epileptic seizures, while alterations in the glutamate-glutamine cycle may be a causative mechanism. These findings provide new insight into the pathogenesis of FSEC and familial mesial temporal lobe epilepsy in human and animals.