RESUMEN
Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.
Asunto(s)
Envejecimiento/genética , Proteína 7 Relacionada con la Autofagia/genética , Disfunción Cognitiva/genética , Suplementos Dietéticos , Proteínas Quinasas/genética , Espermidina/farmacología , Ubiquitina-Proteína Ligasas/genética , Envejecimiento/metabolismo , Animales , Proteína 7 Relacionada con la Autofagia/metabolismo , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Cognición/efectos de los fármacos , Cognición/fisiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/prevención & control , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Aprendizaje/efectos de los fármacos , Aprendizaje/fisiología , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Proteínas Quinasas/metabolismo , Transducción de Señal , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people's everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice.
RESUMEN
A total of six coumarins, bergapten (1), xanthotoxin (2), imperatorin (3), isoimperatorin (4), phellopterin (5) and archangelicin (6), have been isolated from an n-hexane extract of the seeds of Angelica archangelica. The results of comprehensive 2D NMR analyses of archangelicin are discussed.