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1.
Int J Mol Sci ; 25(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38338984

ABSTRACT

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.


Subject(s)
Epilepsy, Temporal Lobe , Epilepsy , Piracetam , Humans , Rats , Animals , Levetiracetam/pharmacology , Levetiracetam/therapeutic use , Epilepsy, Temporal Lobe/chemically induced , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/genetics , Transcriptome , Piracetam/pharmacology , Piracetam/therapeutic use , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Dentate Gyrus
2.
Epilepsy Behav ; 97: 96-104, 2019 08.
Article in English | MEDLINE | ID: mdl-31207446

ABSTRACT

Temporal lobe epilepsy (TLE) is one of the most frequent forms of focal epilepsy; patients with this condition, in addition to exhibiting complex seizures, also exhibit cognitive deficits. In the temporal lobe, the hippocampus, a structure relevant to learning and memory processes, is particularly affected by epilepsy. In animal models of TLE induced by pilocarpine, learning and memory deficiencies associated with changes in synaptic plasticity of the hippocampus have been reported. Cerebrolysin (CBL) is a biologically active mixture of low molecular weight peptides with neuroprotective and neurotrophic effects. The objective of the present study was to determine whether subchronic CBL treatment of rats in the chronic phase of TLE reduces the number and intensity of seizures, and whether CBL treatment can improve cognitive deficits (learning and spatial memory) and dendritic morphology in granular dentate neurons of the hippocampus. Temporal lobe epilepsy (lithium-pilocarpine model) was induced in male Wistar rats (weight, 250-300 g). Two epileptic groups were studied, in which CBL (538 mg/kg) or vehicle was administered intraperitoneally for 5 consecutive days per week for 3 weeks. Respective controls were also included in the study. At the end of treatment, the Barnes maze test (BMT) was used to assess spatial navigational learning and memory. The dendritic morphology of the dentate gyrus was also evaluated using the Golgi-Cox staining method. Results of this study did not support an antiepileptic effect of CBL. Epileptic animals treated with this agent exhibited secondarily generalized seizures similar in frequency and intensity to those of epileptic animals treated only with vehicle. However, when analyzing dendritic morphology of hippocampal granular neurons in these animals, CBL appeared to attenuate dendritic deterioration caused by epilepsy, which was associated with improved cognitive performance of the CBL-treated animals in the BMT compared with vehicle-treated epileptic rats. In conclusion, although CBL did not exert an anticonvulsant effect against secondarily generalized seizures, it can be proposed for use as an add-on therapy in epilepsy management to prevent neuronal alterations, and to improve memory and learning processes.


Subject(s)
Amino Acids/pharmacology , Cognition/drug effects , Dentate Gyrus/drug effects , Epilepsy, Temporal Lobe/physiopathology , Neuronal Plasticity/drug effects , Neurons/drug effects , Neuroprotective Agents/pharmacology , Animals , Cognition/physiology , Cognitive Dysfunction/physiopathology , Dentate Gyrus/cytology , Dentate Gyrus/pathology , Epilepsy, Temporal Lobe/chemically induced , Epilepsy, Temporal Lobe/pathology , Hippocampus/cytology , Hippocampus/drug effects , Hippocampus/pathology , Male , Maze Learning/drug effects , Muscarinic Agonists/toxicity , Neurons/pathology , Pilocarpine/toxicity , Rats , Rats, Wistar , Spatial Memory/drug effects
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