Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11α-hydroxy-erythravine against the pilocarpine model of epilepsy
| Autor: | Daiane Santos Rosa Aguiar, Suelen L Reis, Ana Maria Soares Pereira, Erica Aparecida Gelfuso, Rene Oliveira Beleboni |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Morris water navigation task Hippocampus Convulsants Status epilepticus Hippocampal formation 030226 pharmacology & pharmacy Heterocyclic Compounds 4 or More Rings General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Epilepsy 0302 clinical medicine Alkaloids Status Epilepticus medicine Specific Learning Disorder Animals General Pharmacology Toxicology and Pharmaceutics Cognitive decline Rats Wistar Maze Learning Hippocampal sclerosis Memory Disorders Sclerosis business.industry Dentate gyrus Pilocarpine General Medicine medicine.disease Immunohistochemistry Rats 030104 developmental biology Neuroprotective Agents nervous system medicine.symptom business Neuroscience |
| Zdroj: | Life sciences. 240 |
| ISSN: | 1879-0631 |
| Popis: | Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants. Aims The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance. Main methods Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction. Key findings Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement. Significance Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events. |
| Databáze: | OpenAIRE |
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