Tryptophan-kynurenine pathway metabolite levels were altered in
MTLE-HS
We have also quantified the TKP metabolites namely TRP, KYN, KYNA, QUIN
and neurotransmitters glutamate and GABA in tissues obtained from the
surgically resected hippocampal samples obtained from patients with
MTLE-HS and compared it with autopsy control hippocampus tissues. The
concentration of TRP was significantly reduced (Figure 2a) in the
hippocampal samples. Although KYN concentration was not significantly
altered (Figure 2b), but that of KYNA was significantly reduced in the
hippocampal samples (Figure 2d). The tryptophan kynurenine ratio was
also significantly reduced in the hippocampal samples (Figure 2c). The
concentration of QUIN was significantly enhanced in the hippocampal
samples (Figure 2e). The ratio of QUIN and KYNA was also significantly
enhanced in the hippocampal samples (Figure 2f). The concentration of
glutamate (Figure 2g), GABA (Figure 2h) and glutamate GABA ratio (Figure
2i), neither of those was significantly altered between the two groups.
To investigate the de novo synthesis pattern of KYNA and QUIN in
tissues, 300 µM thick slices were prepared from the surgically resected
hippocampus tissues and tumour periphery non-seizure control tissues,
incubated in ACSF (artificial cerebrospinal fluid) containing 200 µM KYN
(saturating concentration), precursor of both KYNA and QUIN, and
incubated at 30°C in a water bath for 2 hours (Turski et al., 1989). At
the end of the incubation period, the ACSF was aliquoted; KYNA and QUIN
were estimated by HPLC and LC-MS/MS respectively. We observed a similar
pattern of results as earlier. The de novo synthesis of KYNA was
significantly reduced in the hippocampal samples obtained from patients
with MTLE-HS (Figure 2j). Similarly, the de novo synthesis of
QUIN was significantly enhanced in the hippocampal samples obtained from
patients with MTLE-HS (Figure 2k).