Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11 alpha-hydroxy-erythravine against the pilocarpine model of epilepsy

Author(s)

Gelfuso, Erica Aparecida ^[1] ; Reis, Suelen Lorenzato ^[1] ; Soares Pereira, Ana Maria ^[1] ; Rosa Aguiar, Daiane Santos ^[1] ; Beleboni, Rene Oliveira ^{[1, 2]}

Affiliation

^[1] Univ Ribeirao Preto, Dept Biotechnol, Ribeirao Preto, SP - Brazil

^[2] Univ Ribeirao Preto, Sch Med, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 240, JAN 1 2020.
• Web of Science Citations: 0

Abstract

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 ( + )-11 alpha-hydroxy-erythravine, inhibit seizures evoked in rats by different chemo-convulsants. 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 revering 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 ( + )-11 alpha-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. (AU)

• FAPESP's process: 13/13738-8 - Erythrinian alkaloids from E. mulungu Mart. ex Benth. (Leguminosae-Papilionaceae): New assessments on neuroethology, neurochemistry, histology, immunohistochemistry and electroencephalography approaches using rats submitted to pilocarpine model
• Grantee: Erica Aparecida Gelfuso Rossete
• Support Opportunities: Scholarships in Brazil - Doctorate