| Autor: |
de Aquino PEA; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Rabelo Bezerra J; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., de Souza Nascimento T; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Tavares J; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Rosal Lustosa Í; PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, 41121 Modena, Italy., Chaves Filho AJM; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Mottin M; Laboratory of Molecular Modeling and Drug Design, LabMol, Faculty of Pharmacy, Federal University of Goiás, Goiás 74605-050, Brazil., Macêdo Gaspar D; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Andrade GM; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Tavares Neves KR; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil., Biagini G; Laboratory of Experimental Epileptology, Department of Biomedical Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41121 Modena, Italy.; Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41121 Modena, Italy., Silveira ER; Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza 60455-970, Brazil., de Barros Viana GS; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil. |
| Abstrakt: |
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. |
