Reduced endogenous synthesis of KYNA may cause enhanced glutamatergic activity in MTLE-HS
To investigate the role of the endogenously synthesized KYNA on glutamatergic neurotransmission, the tissue slices obtained from patients with MTLE-HS and non-seizure controls were incubated in well carbogenated (95% O2 + 5% CO2) ACSF containing 200 µM KYN (precursor for KYNA) for around 60 mins and then EPSCs were recorded from the pyramidal neurons using the same solution as perfusate for 25 mins (total 85 mins). The reason behind the incubation with KYN was that, it will provide adequate time to synthesize sufficient amount of KYNA which will suppress the glutamatergic events. In the non-seizure control group (n=6), frequency and amplitude of the spontaneous EPSCs were significantly reduced after incubation with 200 µM KYN in comparison to those of basal values (Table 1). The cumulative distribution of inter-event intervals displaced toward longer interval while that of peak amplitudes displaced toward shorter amplitude (Figure 4b and c). Rise time and τdwas not affected (Table 1). In case of the hippocampal samples of the MTLE-HS patients (n=16), the frequency as well as the amplitude of the spontaneous EPSCs were not significantly altered after incubation with 200 µM KYN in comparison to those of basal values (Table 1). The cumulative distribution of inter-event intervals as well as peak amplitudes remain unchanged (Figure 4e and f). Rise time and τd was not affected (Table 1). The magnitude of the percentage reduction of the frequency was significantly reduced in the hippocampal samples in comparison to the non-epileptic controls (51.9± 1.56% in non-epileptic control vs 4.6 ± 0.84% in MTLE-HS; Figure 4g). This result was consistent with above mentioned results that in the hippocampal samples of the MTLE-HS patients, sufficient amount of KYNA is not synthesized from its precursor KYN de novo and consequently enhanced glutamatergic activity was observed.