Protective effects against memory impairment induced by methylglyoxal in mice co­treated with FPS­ZM1, an advanced glycation end products receptor antagonist.

Memory impairment is a feature of several diseases and detrimental as aging population have increased worldwide. Sustained advanced glycation end products (AGEs) receptor (RAGE) activation triggers the production of reactive oxygen species and inflammatory response, leading to neuronal dysfunction and neurodegenerative disorders. Methylglyoxal (MGO) is the most relevant and reactive glycating agent in vivo, leading to the formation of AGEs. Here, we investigated the role of RAGE on the memory impairment induced by MGO. Swiss female mice were treated for 11 days with MGO, FPS­ZM1 (a high­affinity RAGE antagonist), or the combination of both. Locomotor activity was not impaired by the treatments, as evaluated by the open field and spontaneous alternation test. MGO treatment impaired short­ and long­term spatial memory in the object location task, caused deficits on the short­term aversive memory in the step­down inhibitory avoidance task, and decreased working memory performance as evaluated by the Y­maze spontaneous alternation test. FPS­ZM1 treatment abolished deficits on the short­term aversive memory and working memory, but was unable to prevent the impairment in short­term or long­term spatial memory. Since the addition of RAGE antagonist in co­treatment with MGO protected mice from the aversive and working memory deficits, AGEs generated by the MGO treatment would be involved in the memory impairment due to RAGE activation. Therefore, further studies are required to establish the involvement of RAGE in the MGO­induced memory impairment. Nevertheless, our results suggested FPS­ZM1 treatment as a promising new therapeutic strategy to prevent cognitive dysfunction caused by dicarbonyl stress, further investigation is required to confirm our findings.

Antidepressant-like effect of hydroalcoholic extract from barks of Rapanea ferruginea: Role of monoaminergic system and effect of its isolated compounds myrsinoic acid A and B.

Major Depressive Disorder (MDD) is a highly disabling condition and has been linked to increased inflammatory mediators. Hydroalcoholic extract from barks of Rapanea ferruginea (HEBRF) and the majoritary compounds-myrsinoic acid A (MAA) and B (MAB)-have been studied due to their anti-inflammatory potential, but there is no evidence about its antidepressant-like effects. This research investigated the HEBRF, MAA, and MAB antidepressant-like effect, besides the involvement of the monoaminergic system and MAO-A activity in the HEBRF antidepressant-like effect. HEBRF (50-300 mg/kg, p.o.), MAA (5-30 mg/kg, p.o.) or MAB (3-60 mg/kg, p.o.) were administrated to mice, and behavioral parameters were assessed using the tail suspension test (TST), splash test (ST) and open field test (OFT). The involvement of monoaminergic system in the HEBRF antidepressant-like effect was established through the pretreatment of mice with antagonists. The influence triggered by HEBRF in the monoamine oxidase A (MAO-A) activity was evaluated in the hippocampus (HIP) and prefrontal cortex (PFC) of mice. HEBRF (100-300 mg/kg) promoted antidepressant-like effect in the TST and augmented the total time of grooming in the ST, without compromising the locomotor activity. Pretreatment of mice with serotoninergic, dopaminergic, and noradrenergic antagonists, reversed the HEBRF antidepressant-like effect. Besides, HEBRF inhibited the MAO-A activity in the HIP and PFC. Moreover, MAA (5 mg/kg) and MAB (3 mg/kg) also promoted antidepressant-like and anti-anhedonic effects in mice. Data showed that monoaminergic system is involved in the HEBRF antidepressant-like effect, besides MAA and MAB possibly could be responsible for these pharmacological effects.