RESUMEN
BACKGROUND: Mutations in the human Ubiquilin 2 gene are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD), the fatal neurodegenerative disease that progressively affected neuronal cells in both brain and spinal cord. There is currently no effective therapy for these diseases. Over the last decade, researchers have focused on the potential use of natural products especially in neurodegenerative studies. Insect products have been used as traditional medicines, however, scientific information is still lacking. Fruit fly is recently used as a model organism to investigate degenerative diseases related to the nervous system because it has a short life span and produces a large number of offspring. METHODS: The present study investigated the effects of honeybee products and edible insect powders on the locomotive and learning abilities, neuromuscular junctions (NMJs) structure, and reactive oxygen species (ROS) in larval brains of Ubiquilin- knockdown Drosophila. RESULTS: dUbqn knockdown flies showed defects in locomotive and learning abilities accompanied with structural defects in NMJs. The results obtained revealed that the recovery of locomotive defects was significantly greater in dUbqn knockdown flies fed with coffee honey from Apis cerana (1% v/v) or Apis dorsata melittin (0.5 µg/ml) or wasp powder (2 mg/ml) than that of in untreated dUbqn knockdown flies. Furthermore, dUbqn knockdown flies fed with coffee honey showed the partial rescue of structural defects in NMJs, improved learning ability, and reduced the accumulation of ROS caused by dUbqn depletion in the brain over the untreated group. CONCLUSION: These results suggest that coffee honey from Apis cerana contains a neuroprotective agent that will contribute to the development of a novel treatment for ALS/FTD.
Asunto(s)
Apiterapia/métodos , Insectos Comestibles , Locomoción/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Abejas , Drosophila , Femenino , Polvos , TailandiaRESUMEN
Bacopa monnieri L. Wettst. (BM) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function. We previously reported that administration of BM alcoholic extract (BME) prevents trimethyltin (TMT)-induced cognitive deficits and hippocampal cell damage and promotes TMT-induced hippocampal neurogenesis. In this study, we demonstrate that administration of BME improves spatial working memory in adolescent (5-week- old) healthy mice but not adult (8-week-old) mice. Moreover, improved spatial working memory was retained even at 4 weeks after terminating 1-week treatment of adolescent mice. One-week BME treatment of adolescent mice significantly enhanced hippocampal BrdU incorporation and expression of genes involved in neurogenesis determined by RNAseq analysis. Cell death, as detected by histochemistry, appeared not to be significant. A significant increase in neurogenesis was observed in the dentate gyrus region 4 weeks after terminating 1-week treatment of adolescent mice with BME. Bacopaside I, an active component of BME, promoted the proliferation of neural progenitor cells in vitro in a concentration-dependent manner via the facilitation of the Akt and ERK1/2 signaling. These results suggest that BME enhances spatial working memory in healthy adolescent mice by promoting hippocampal neurogenesis and that the effects of BME are due, in significant amounts, to bacopaside I.
Asunto(s)
Bacopa/química , Giro Dentado/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Memoria a Corto Plazo/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Nootrópicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Memoria Espacial/efectos de los fármacos , Animales , Células Cultivadas , Replicación del ADN/efectos de los fármacos , Giro Dentado/fisiopatología , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Medicina Ayurvédica , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/fisiopatología , Ratones , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/genética , Nootrópicos/farmacología , Extractos Vegetales/farmacología , RNA-Seq , Saponinas/farmacología , Maduración Sexual , Transducción de Señal/efectos de los fármacos , Compuestos de Trimetilestaño/toxicidad , Triterpenos/farmacologíaRESUMEN
The relationship between oxidative stress and neurodegenerative diseases has been extensively examined, and antioxidants are considered to be a promising approach for decelerating disease progression. Parkinson's disease (PD) is a common neurodegenerative disorder and affects 1% of the population over 60 years of age. A complex combination of genetic and environmental factors contributes to the pathogenesis of PD. However, since the onset mechanisms of PD have not yet been elucidated in detail, difficulties are associated with developing effective treatments. Curcumin has been reported to have neuroprotective properties in PD models induced by neurotoxins or genetic factors such as α-synuclein, PINK1, DJ-1, and LRRK2. In the present study, we investigated the effects of curcumin in a novel Drosophila model of PD with knockdown of dUCH, a homolog of human UCH-L1. We found that dopaminergic neuron-specific knockdown of dUCH caused impaired movement and the loss of dopaminergic neurons. Furthermore, the knockdown of dUCH induced oxidative stress while curcumin decreased the ROS level induced by this knockdown. In addition, dUCH knockdown flies treated with curcumin had improved locomotive abilities and less severe neurodegeneration. Taken together, with studies on other PD models, these results strongly suggest that treatments with curcumin are an appropriate therapy for PD related to oxidative stress.