BACKGROUNDNa + /Ca 2+ exchanger (NCX) plays a crucial role in pentylenetetrazol-induced convulsion. However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion. In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion.

METHODSTwenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group (n = 7 in each group). Whole-cell patch-clamp method was used to record NCX currents. Both the Western blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3.

RESULTSNCX currents were decreased in rats after febrile convulsion. Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively. Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures.

CONCLUSIONSThere is a significant reduction in NCX3 expression in rats with febrile convulsions. Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.

Animals ; Cerebral Cortex ; metabolism ; Down-Regulation ; Female ; Fever ; complications ; Hippocampus ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Seizures ; etiology ; metabolism ; Sodium-Calcium Exchanger ; metabolism

OBJECTIVETo investigate effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats.

METHODSChronic transauricular kindled seizures was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. A passive avoidance test was used to measure memory retention ability. Morphological changes in neurons of hippocampal CA1 region was examined after HE staining. Histamine, gamma-aminobutyric acid (GABA) and glutamate levels in the hippocampus were measured by high performance liquid chromatography (HPLC).

RESULTChronic transauricular kindled seizures impaired passive-avoidance test memory retention in rats. The damaged CA1 neurons were observed and histamine content in the hippocampus markedly decreased 24 h after the end of kindling in the chronic transauricular kindled rats.

CONCLUSIONChronic transauricular kindled seizure impaired passive-avoidance test memory retention, and it might be due to the damaged CA1 neurons and a decrease of histamine in the hippocampus induced by epilepsy.

Animals ; Avoidance Learning ; Hippocampus ; metabolism ; pathology ; physiopathology ; Histamine ; metabolism ; Kindling, Neurologic ; Male ; Memory Disorders ; etiology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Seizures ; metabolism ; pathology ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo investigate effects of acute maximal electroshock (MES) and chronic transauricular kindled seizures on learning abilities in Sprague-Dawley rats.

METHODSAn acute MES was induced by giving an alternating current (150 mA, 0.2 s) through ear-clip electrodes. Chronic transauricular kindled seizure was induced by repeated application of initially subconvulsive electrical stimulation (40 mA, 0.2 s) through ear-clip electrodes once every 24 h. An 8-arm radial maze (4 arms baited) was used to measure learning abilities. Histamine, glutamate and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography (HPLC).

RESULTIn the acquisition learning process, an acute MES increased reference memory errors but not working memory errors. In addition, it increased GABA levels in the hippocampus. On the other hand, chronic transauricular kindled seizures increased both working and reference memory errors in retrieval memory process, and this lasted for at least 3 weeks. Chronic transauricular kindled seizures induced CA1 neuron damage and a decrease in histamine levels in the hippocampus.

CONCLUSIONDifferent types of kindling seizure produce different effects on cognitive behavior: (1) an acute MES impairs learning ability, which may be associated with an abnormal plasticity and an increase of GABA in the hippocampus; (2) the chronic transauricular kindled seizure impairs retrieval memory mainly, which may be related to CA1 neuron damage and a decrease in histaminergic activity in the hippocampus.

Animals ; Chronic Disease ; Electric Stimulation ; instrumentation ; methods ; Electrodes ; Electroshock ; adverse effects ; Hippocampus ; metabolism ; Histamine ; metabolism ; Kindling, Neurologic ; physiology ; Learning Disorders ; etiology ; metabolism ; physiopathology ; Maze Learning ; physiology ; Memory Disorders ; etiology ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Seizures ; complications ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

Repeated electroconvulsive seizure (ECS), a model for electroconvulsive therapy (ECT), exerts neuroprotective and proliferative effects in the brain. This trophic action of ECS requires inhibition of apoptotic activity, in addition to activation of survival signals. c-Myc plays an important role in apoptosis of neurons, in cooperation with the Bcl-2 family proteins, and its activity and stability are regulated by phosphorylation and ubiquitination. We examined c-Myc and related proteins responsible for apoptosis after repeated ECS. In the rat frontal cortex, repeated ECS for 10 days reduced the total amount of c-Myc, while increasing phosphorylation of c-Myc at Thr58, which reportedly induces degradation of c-Myc. As expected, ubiquitination of both phosphorylated and total c-Myc increased after 10 days ECS, suggesting that ECS may reduce c-Myc protein level via ubiquitination-proteasomal degradation. Bcl-2 family proteins, caspase, and poly(ADP-ribose) polymerase (PARP) were investigated to determine the consequence of down-regulating c-Myc. Protein levels of Bcl-2, Bcl-X(L), Bax, and Bad showed no change, and cleavage of caspase-3 and PARP were not induced. However, phosphorylation of Bad at Ser-155 and binding of Bad to 14-3-3 increased without binding to Bcl-X(L) after repeated ECS, implying that repeated ECS sequesters apoptotic Bad and frees pro-survival Bcl-X(L). Taken together, c-Myc down-regulation via ubiquitination-proteasomal degradation and Bad inactivation by binding to 14-3-3 may be anti-apoptotic mechanisms elicited by repeated ECS in the rat frontal cortex. This finding further supports the trophic effect of ECS blocking apoptosis as a possible therapeutic effect of ECT.
14-3-3 Proteins/metabolism ; Animals ; Down-Regulation ; Electroconvulsive Therapy/*adverse effects ; Frontal Lobe/*metabolism ; Male ; Models, Biological ; Neurons/metabolism ; Periodicity ; Phosphorylation ; Protein Binding ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-myc/*metabolism ; Rats ; Rats, Sprague-Dawley ; Seizures/etiology/*metabolism ; Tumor Cells, Cultured ; Ubiquitination ; bcl-Associated Death Protein/antagonists & inhibitors/*metabolism