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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Alzheimer's disease (AD) is an age‐related neurodegenerative disease characterized by a progressive decline in cognitive functions. Adenosine receptors play a pivotal role in disease progression, however, adenosine A3 receptors are understudied and their effects vastly unknown. We now investigated the effects of the activation of adenosine A3 receptors on memory deficits and oxidative damage in a mouse model of streptozotocin‐induced experimental dementia of Alzheimer's type. Male Swiss mice received bilateral intracerebroventricular injections of streptozotocin (STZ, 3 mg/kg) dissolved in artificial cerebrospinal fluid. Two days after the first STZ administration, injections were repeated, and the animals were treated with the A3 receptor agonist, CF102 (200 μg/kg intraperitoneally), or vehicle (2% DMSO in saline), 1 h after surgery and once a day until the last day of behavioral evaluation (18th after the first STZ injection). The animals subjected to STZ administration showed significant recognition memory deficits evaluated by the object recognition task, spatial memory deficits evaluated by water maze test, and early and late memory deficits in the passive avoidance test. No differences of locomotor activity in the open field test were observed between groups. STZ also increased malonaldehyde and nitrite contents in the hippocampus. The treatment with CF102 significantly prevented the early and late memory deficits and object recognition memory deficits. CF102 treatment also reduced the increase of nitrite production in 37% in the hippocampus when compared to STZ group. These data highlight the therapeutic potential of A3 agonists in AD, however the role of these receptors on STZ‐induced AD model requires more investigation.Support or Funding InformationSupported by Brazilian National Research and Development Council (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES) ‐ Brazil, and the Research Support Foundation of Ceará (FUNCAP) – Brazil.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Brain ischemia pathophysiology involves a complex cascade of events such as inflammation and oxidative stress that lead to neuronal loss and cognitive deficits. (−)‐α‐Bisabolol is a sesquiterpene alcohol obtained from plants such as Vanillosmopsis erythropappa and Matricaria chamomilla, with anti‐inflammatory and antioxidant properties. The present study aimed to investigate the effects of (−)‐α‐Bisabolol (α‐Bis) on neuronal damage and memory deficits induced by permanent middle cerebral artery occlusion (MCAO). Mice were submitted to MCAO and were treated with α‐Bis (50, 100, and 200mg/kg, orally), 3 hours after MCAO and during 4 days. The parameters studied were: infarcted area, memory deficits, myeloperoxidase (MPO) activity, and immunoreactivity for cytochrome C, NF‐κB, and superoxide dismutase (SOD‐2). α‐Bis treatment reduced significantly cerebral infarction, neurological and aversive memory deficits, decreased MPO, and cytochrome c, NF‐κB and SOD‐2 immunoreactivity when compared with MCAO group. Taken together, our study demonstrated neuroprotective effect of (−)‐α‐Bisabolol against ischemia‐induced cerebral injury in mice. We propose that the neuroprotection offered by (−)‐α‐Bisabolol can be attributed, at least in part, to its anti‐inflammatory activity.Support or Funding InformationFUNCAP, UFCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.