ABSTRACT
OBJECTIVE: The mechanisms behind seizure suppression by deep brain stimulation (DBS) are not fully revealed, and the most optimal stimulus regimens and anatomical targets are yet to be determined. We investigated the modulatory effect of low-frequency DBS (L-DBS) in the ventral tegmental area (VTA) on neuronal activity in downstream and upstream brain areas in chemically kindled mice by assessing c-Fos immunoreactivity. MATERIALS AND METHODS: In this experimental study, 4-6 weeks old BL/6 male mice underwent stereotaxic implantation of a unilateral stimulating electrode in the VTA followed by pentylenetetrazole (PTZ) administration every other day until they showed stage 4 or 5 seizures following 3 consecutive PTZ injections. Animals were divided into control, sham-implanted, kindled, kindled-implanted, L-DBS, and kindled+L-DBS groups. In the L-DBS and kindled+L-DBS groups, four trains of L-DBS were delivered 5 min after the last PTZ injection. 48 hours after the last L-DBS, mice were transcardially perfused, and the brain was processed to evaluate c-Fos expression by immunohistochemistry. RESULTS: L-DBS in the VTA significantly decreased the c-Fos expressing cell numbers in several brain areas including the hippocampus, entorhinal cortex, VTA, substantia nigra pars compacta, and dorsal raphe nucleus but not in the amygdala and CA3 area of the ventral hippocampus compared to the sham group. CONCLUSION: These data suggest that the possible anticonvulsant mechanism of DBS in VTA can be through restoring the seizure-induced cellular hyperactivity to normal.
ABSTRACT
INTRODUCTION: Several studies indicate erythropoietin (Epo) to have remarkable neuroprotection in various central nervous system disorders, including Alzheimer's disease (AD). Amyloid beta (Aß) is believed to be responsible for the synaptic dysfunction that occurs in AD. Therefore, the present study is aimed to investigate the effects of Epo on the Aß-induced impairments in learning-memory and hippocampal synaptic plasticity. MATERIALS AND METHODS: Male Sprague-Dawley rats (200-250 g) were used in this study. After the injection of Aß, they were injected intra-peritoneal with Epo in the Aß+Epo group or its vehicle in the Aß+V group every other day for 12 days. A shuttle box apparatus was used for the passive avoidance learning and memory study. Moreover, paired-pulse ratio (PPR) was monitored before and after tetanic stimulation. RESULTS: Bilateral injection of Aß decreased step-through latency (STL), whereas the 12 day administration of Epo significantly improved memory performance in Aß+Epo group. The field potential recording demonstrated that the in vivo administration of Aß25-35 led to extreme inhibition in long-term potentiation, this inhibition was accompanied by a significant increase of the normalized PPR (PPR after HFS/PPR before HFS) as an index for release probability. However, administration of Epo recovers the magnitude of the LTP and the extent of normalized PPR. CONCLUSION: The results of this study demonstrated that the injection of Aß25-35 resulted in impaired LTP and the memory process, which is likely mediated through increasing the release probability of neurotransmitter vesicles. In addition, treatment with Epo improved the Aß-induced deficits in memory and LTP induction, probably via recovering the release probability.
