a proline derivative-enriched fraction from sideroxylon obtusifolium protects the hippocampus from intracerebroventricular pilocarpine-induced injury associated with status epilepticus in mice

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ID: 135265
2020
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Abstract
The N-methyl-(2S,4R)-trans-4-hydroxy-l-proline-enriched fraction (NMP) from Sideroxylon obtusifolium was evaluated as a neuroprotective agent in the intracerebroventricular (icv) pilocarpine (Pilo) model. To this aim, male mice were subdivided into sham (SO, vehicle), Pilo (300 µg/1 µL icv, followed by the vehicle per os, po) and NMP-treated groups (Pilo 300 µg/1 µL icv, followed by 100 or 200 mg/kg po). The treatments started one day after the Pilo injection and continued for 15 days. The effects of NMP were assessed by characterizing the preservation of cognitive function in both the Y-maze and object recognition tests. The hippocampal cell viability was evaluated by Nissl staining. Additional markers of damage were studied—the glial fibrillary acidic protein (GFAP) and the ionized calcium-binding adaptor molecule 1 (Iba-1) expression using, respectively, immunofluorescence and western blot analyses. We also performed molecular docking experiments revealing that NMP binds to the γ-aminobutyric acid (GABA) transporter 1 (GAT1). GAT1 expression in the hippocampus was also characterized. Pilo induced cognitive deficits, cell damage, increased GFAP, Iba-1, and GAT1 expression in the hippocampus. These alterations were prevented, especially by the higher NMP dose. These data highlight NMP as a promising candidate for the protection of the hippocampus, as shown by the icv Pilo model.
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aquino2020internationala Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Pedro Everson Alexandre de Aquino;Jéssica Rabelo Bezerra;Tyciane de Souza Nascimento;Juliete Tavares;Ítalo Rosal Lustosa;Adriano José Maia Chaves Filho;Melina Mottin;Danielle Macêdo Macêdo Gaspar;Geanne Matos de Andrade;Kelly Rose Tavares Neves;Giuseppe Biagini;Edilberto Rocha Silveira;Glauce Socorro de Barros Viana
Journal Intertax
Year 2020
DOI
10.3390/ijms21114188
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