Search

In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT 1A receptors in mediating LFS’ improving effect on spatial learning and memory was investigated in amygdala-kindled rats. Amygdala kindling was conducted in a semi-rapid kindling stimulations (12 stimulations per day) in male Wistar rats. LFS (4 trains of 0.1 ms pulse duration at 1 Hz, 200 pulses, 50–150 μA, at 5 min intervals) was applied after termination of kindling stimulations. NAD-299 (a selective 5-HT 1A receptor antagonist; 2.5 and 5 μg/μl) was microinjected into the hippocampal CA1 before applying LFS. The Morris water maze, and novel object recognition tests were conducted after the last kindling stimulation. Hippocampal samples were also prepared, and 5-HT 1A receptor gene expression levels were assessed using quantitative RT-PCR. In kindled animals, LFS reduced impairments in spatial learning and memory in the Morris water maze and novel object recognition tests. Microinjection of NAD doses of 5 μg/μl reduced the effects of LFS on learning and memory. The gene expression level of 5-HT 1A receptors increased significantly in the hippocampus of amygdala-kindled rats. However, LFS applied after kindling stimulations inhibited this effect. It seems that activation of 5-HT 1A receptors in the CA1 field is necessary for LFS’ improving effects on spatial learning and memory in kindled animals; although surprisingly, LFS application prevented the elevation in gene expression of 5-HT 1A receptors in kindled animals. © 2019 Elsevier Inc.

Kindling results in abnormal synaptic potentiation and significant impairment in learning and memory. Electromagnetic field (EMF) effects on learning and memory in kindled animals and its effects on hippocampal neural activity are largely unknown. In the current study, the effects of EMF on learning and memory, as well as hippocampal synaptic plasticity, in kindled rats were investigated. EMF (10 mT; 100 Hz) was applied to fully kindled animals one hour/day for a period of one week. The behavioral and electrophysiological studies were performed 24 h following the EMF application. The kindled rats showed spatial learning deficits during the training phase of the Morris water maze (MWM) test. Moreover, there were increments in escape latency and path length compared to the sham group. The kindled rats spent less time in the target-quadrant probe test, indicating spatial memory impairment. Applying EMF to the KEMF group (kindling + EMF) restored learning and memory, and decreased escape latency and path length significantly compared to the kindled group. EMF alone had no significant effects on the learning and memory parameters. Based on the open field (OF) test results, EMF alone in the EMF group, but not in the kindled or the KEMF groups, decreased the total traveled distance and increased the spent time in the peripheral zone, compared to the sham group. Based on electrophysiological results, applying EMF in the KEMF group returned the ability of synaptic potentiation to the hippocampal CA1 area and high-frequency stimulation induced long-term potentiation (LTP). Accordingly, EMF can be considered a potential therapy for seizure-induced deficits in learning and memory.

Introduction The signaling pathways involved in the antiepileptogenic effect of low frequency electrical stimulation (LFS) have not been fully understood. In the present study the role of extracellular signal-regulated kinase (ERK) signaling cascade was investigated in mediating the inhibitory effects of LFS on kindled seizures. Methods Animals received kindling stimulations for seven days (the mean number of stimulation days for achieving stage 5 seizure) according to semi-rapid perforant path kindling protocol (12 stimulations per day at 10 min intervals). LFS (0.1 ms pulse duration at 1 Hz, 800 pulses) was applied at 5 min after the last kindling stimulation every day. During the kindling procedure, FR180204 (inhibitor of ERK) was daily microinjected (1 μg/μl; intracerebroventricular) immediately after the last kindling stimulation and before LFS application. The expression of activated ERK (p-ERK) in the dentate gyrus was also investigated using immunohistochemistry technique. Results Application of LFS at 5 min after the last kindling stimulation had inhibitory effect on kindling rate. FR180204 had no significant effect on seizure parameters when administered at the dose of 1 μg/μl in kindled group of animals. However, microinjection of FR180204 before LFS application reduced the inhibitory effect of LFS on seizure severity and field potential parameters (i.e. the slope of population field excitatory postsynaptic potentials and population spike amplitude) during kindling. FR180204 also blocked the preventing effects of LFS on kindling-induced increase in early (at 10–40 ms intervals) and late (at 300–1000 ms intervals) paired pulse depression. In addition, application of LFS following kindling stimulations increased the expression of p-ERK in the dentate gyrus. Conclusion Obtained results showed ERK signaling pathway had important role in mediating the antiepileptogenic effect of LFS in perforant path kindling. These findings represent a promising opportunity to gain insight about LFS mechanism in epilepsy therapy.

In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT