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.