ANTIEPILEPTIC EFFECT OF THE ACYLPOLYAMINETOXIN JSTX-3 IN HUMAN HIPPOCAMPAL CA1 NEURONS [italic]IN VITRO[/italic]
Abstract number :
1.052
Submission category :
Year :
2004
Submission ID :
4153
Source :
www.aesnet.org
Presentation date :
12/2/2004 12:00:00 AM
Published date :
Dec 1, 2004, 06:00 AM
Authors :
1Simone D. Salamoni, 1,2,3Jaderson C. Da Costa, 4Mario Sergio Palma, 4,5Katsuhiro Konno, 2Ney A.V. Azambuja, 2Eliseu Paglioli-Neto, 1Andrea A. Tavares, 1Daniela S. Abr
The Spider toxin JSTX is an acylpolyaminetoxin that blocks the postsynaptic glutamate synapse in hippocampal pyramidal neurons (Brain Research 1985;346:397-399). Since glutamatergic receptors are involved in the epilepsy physiopathology, the aim of this study was to verify a possible effect of the synthetic acylpolyaminetoxin JSTX-3 on epileptogenic discharges induced by perfusion of human hippocampal slices with a free-magnesium medium. Hippocampal samples from seven patients with medically refractory mesial temporal lobe epilepsy underwent surgical treatment were collected. The hippocampal tissue was sliced in 500 mm coronal sections. The slices (n:7) were kept in a prechamber at room temperature in Ringer, which was continuously bubbled with 95% O2, 5% CO2. The slices were then transferred into an interface recording chamber continuously perfused with an oxygenated Ringer solution. Intra- and extracellular recordings were simultaneously obtained from CA1 pyramidal neurons. Ictal-like activity and interictal discharges were induced by perfusing the slice with oxygenated Magnesium-free Ringer solution. In all neurons (n:10) the epileptogenic activity was blocked with the application of JSTX-3 toxin. This effect was similar to the one obtained for 2-amino-5-phosphonovaleric acid (APV) perfusion. Recurrent epileptiform discharges were induced by iontophoretic application of N-methyl-D-aspartate (NMDA) and they were also blocked by the JSTX-3 pressure ejection. Our findings suggest that the synthetic acylpolyaminetoxin JSTX-3 has an antiepileptic effect on CA1 human hippocampal neurons. (Supported by CAPES, CNPq, FAPERGS, PUCRS, Secretaria de C[amp]T do RS, CAT/CEPID- FAPESP.)