Changes in functional coupling of 5-HT1A receptor to the G-protein in neocortex temporal tissues of patients with temporal lobe epilepsy

Abstract

Background

The 5-hydroxytryptamine-1A receptors are known to be involved in the inhibition of seizures in epilepsy.

Objective

The main aim of the present study is to determine the functional coupling to G-protein of the 5-HT_1A receptor through 8-OH-DPAT-stimulated [³⁵S]GTPγS binding assay in lateral temporal neocortex tissue of patients with mesial temporal lobe epilepsy (mTLE) and correlate it with clinical data.

Material and methods

The activation of the G protein complex was determined by [³⁵S]GTPγS binding assay. The temporal neocortex tissue was obtained from 5 patients with mTLE during epilepsy surgery and from 5 subjects (autopsies) who died due to an accident and without history of neurological disease.

Results

We found that values of maximal stimulation (E_max) of [³⁵S]GTPγS binding significant decreased in the mTLE group (30.8%, p < .05) when compared to the autopsy samples (65.9%). The values of potency (pEC₅₀) were similar in both groups. However, we found no significant differences between the E_max and age of patient, age of seizure onset, duration of epilepsy and frequency of seizures. Also, the pEC₅₀ values revealed no significant correlations with the clinical data.

Conclusions

Our data provide evidence that the lateral temporal neocortex of patients with pharmacoresistant mTLE presents alterations in the functional coupling to G-protein of the 5-HT_1A receptor. Such a change could be involved in hyperexcitability in the neocortex of patients with mTLE.