Alteration in NCX-3 immunoreactivity within the gerbil hippocampus following spontaneous seizures

Abstract

Although NCX-3 is highly expressed in the brain, the distribution of NCX-3 in the epileptic hippocampus is still controversial. Therefore, to assess the distribution and pattern of NCX-3 expression in epileptic hippocampus, we performed a comparative analysis of NCX-3 immunoreactivities in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. In SR gerbils, NCX-3 immunoreactivity was higher than pre-seizure SS gerbils, particularly in the pavalbumin (PV)-positive interneurons. Three h post-ictal, NCX-3 immunoreactivity in the SS gerbil hippocampus was markedly elevated to the level of SR gerbils. Six h post-ictal, the expression of NCX-3 was reduced to the level of pre-seizure SS gerbils. Therefore, the results of the present study suggest that down-regulation of NCX-3 expression in the SS gerbil hippocampus may be involved in the hyperexcitability of SS gerbils due to an imbalance of intracellular Na

Decreased expression of hippocampal Na+/Ca2+ exchanger isoform-1 by pentylenetetrazole kindling in mice

“…This finding suggests that downregulation of hippocampal NCX3 is involved in the hyperexcitability of seizure-sensitive gerbils. The different results between the previous and present studies could be explained by the animal models used: Park et al (2011) used the inherited epilepsy model in gerbils, while we used a PTZ-induced kindling model in mice. Since their immunohistochemical study focused on expression of NCX3 in the hippocampus of the gerbils, it is not known whether NCX1 plays a key role in the hyperexcitability of seizure-sensitive gerbils.…”

“…We found that hippocampal NCX3 expression, unlike that of NCX1 and NCX2, was not altered by chronic administration of PTZ. In contrast, Park et al (2011) reported that NCX3 may be involved in the pathogenesis of tonic-clonic seizures in Mongolian gerbils, a model of inherited epilepsy. They showed that NCX3 immunoreactivity in seizure-resistant gerbils was higher than in pre-seizure seizuresensitive gerbils, and in the seizure-sensitive gerbil hippocampus NCX3 immunoreactivity after seizure was increased to the level of seizure-resistant gerbils.…”

Altered expression of adrenocorticotropic hormone in the epileptic gerbil hippocampus following spontaneous seizure

“…(9) and other previous studies (14, 15). Only animals with a consistent stage 4 or 5 seizure score according to the seizure severity rating scale of Loskota et al (34) were included in the present study, and were described as seizure sensitive (SS, n = 10) gerbils.…”

“…and perfused transcardially with phosphate-buffered saline (PBS, pH 7.4) followed by 4% paraformaldehyde in 0.1 M PBS. After this, tissue processing and immunohistochemistry processes were performed according to pervious described studies (14, 15). The sections were firstly incubated in mouse anti-ACTH antiserum (diluted 1：400; Peninsula, USA) containing 0.3% Triton X-100 and 2% normal goat serum overnight at room temperature.…”

“…The seizures exhibited by gerbils are consistent over time, so it is possible to correlate seizure intensity records with morphological observations (9,11-15). Previous studies have focused on the role of CRF, the regulator of pituitary ACTH release, in epileptic mechanisms (16,17).…”