Discussion
The present results demonstrate that (i) endogenous synthesis of KYNA, a
glutamate receptor inhibitor, was lowered in the hippocampal samples
obtained from patients with MTLE-HS, possibly due to reduced levels of
the enzyme KAT II and its co-factor PLP. (ii) Reduced endogenous KYNA
levels may contribute to the maintenance of enhanced synaptic
glutamatergic activity on to the pyramidal neurons in slice preparations
of the resected hippocampal samples obtained from patients with MTLE-HS.
(iii) Under resting conditions, the effect of the reduced endogenous
KYNA levels could be attributed to both pre- as well as post-synaptic
regulation of glutamatergic activity. (iv) Endogenous synthesis of QUIN
was elevated in the hippocampal samples obtained from patients with
MTLE-HS. These concepts can help explain the potential contribution of
TKP metabolites to hyperexcitability associated with MTLE-HS.