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.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
de Aquino PEA,Rabelo Bezerra J,de Souza Nascimento T,Tavares J,Rosal Lustosa Í,Chaves Filho AJM,Mottin M,Macêdo Gaspar D,Andrade GM,Tavares Neves KR,Biagini G,Silveira ER,de Barros Viana GSdoi
10.3390/ijms21114188subject
Has Abstractpub_date
2020-06-11 00:00:00issue
11issn
1422-0067pii
ijms21114188journal_volume
21pub_type
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