RESUMEN
Depression is a prevalent mental illness, affecting a significant portion of the global population. Recent research has highlighted the crucial role of the gut microbiota in both metabolic and central nervous health. By reviewing literature from various databases, including Pubmed, Science Direct, Web of Science, and Scopus, spanning the years 2005-2023, a comprehensive search was conducted using keywords such as "Depression" and "Gut Microbiota". The gut microbiota acts as a "second brain" in humans and can communicate bidirectionally with the brain through the Brain-gut-microbiota axis pathway. This communication involves the immune and nervous systems. However, there are challenges in detecting and treating depression effectively. To address these limitations, researchers have been exploring the relationship between gut microbiota and depression. Studies have shown that gut microbial metabolites, such as lipopolysaccharides and short-chain fatty acids, can induce pro-inflammatory cytokines that contribute to neuroinflammation and increase the risk of depression. The kynurenine pathway, triggered by gut microbial metabolites, has also been associated with neuroinflammation. Thus, investigating these microbial metabolites can provide insights into depression treatment. This review focuses on analyzing the connection between gut microbial metabolites, inflammation, and depression. It explores novel mechanisms contributing to depression, specifically focusing on the mediation of inflammation through the release of pro-inflammatory cytokines. The objective is to provide valuable insights into the mechanisms underlying depression and to propose potential treatments.
Asunto(s)
Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Depresión , Enfermedades Neuroinflamatorias , Inflamación , CitocinasRESUMEN
Recently, the underlying mechanisms of acupuncture on the effects of Alzheimer's disease (AD) treatment have not been fully elucidated. Defects in ALP (autophagy-lysosomal pathway) and TFEB (transcription factor EB) play critical roles in AD. Our previous studies have demonstrated that electroacupuncture (EA) can ameliorate both ß-amyloid (Aß) pathology and cognitive function in APP/PS1 mice. However, the effects of EA on the expression of ALP and TFEB and their potential mechanisms require further investigation. Twenty-eight male APP/PS1 mice were randomly divided into Tg and Tg + EA groups, and 14 C57BL/6 mice served as the wild-type (WT) group. After 1 week of adaptation to the living environment, mice in the Tg + EA group were restrained in mouse bags and received manual acupuncture at Baihui (GV20) acupoint and EA stimulation at bilateral Yongquan (KI1) acupoints, using the same restraint method for WT and Tg groups. The intervention was applied for 15 min each time, every other day, lasting for six weeks. After intervention, the spatial learning and memory of the mice was assessed using the Morris water maze test. Hippocampal Aß expression was detected by immunohistochemistry and ELISA. Transmission electron microscopy (TEM) was used to observe autophagic vacuoles and autolysosomes in the hippocampus. Immunofluorescence method was applied to examine the expression of TFEB in CA1 region of the hippocampus and the co-localization of CTSD or LAMP1 with Aß. Western blot analysis was performed to evaluate the changes of LC3, p62, CTSD, LAMP1, TFEB and n-TFEB (nuclear TFEB) in the hippocampus. The findings of behavioral assessment indicated that EA alleviated the cognitive impairment of APP/PS1 mice. Compared with the WT group, the Tg group showed significant cognitive decline and abnormalities in ALP and TFEB function (P < 0.01 or P < 0.05). However, these abnormal changes were alleviated in the Tg + EA group (P < 0.01 or P < 0.05). The Tg group also showed more senile plaques and ALP dysfunction features, compared with the WT group, and these changes were alleviated by EA. In conclusion, this study highlights that EA ameliorated Aß pathology-related cognitive impairments in the APP/PS1 model associated with ALP and TFEB dysfunction.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Electroacupuntura , Animales , Masculino , Ratones , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Disfunción Cognitiva/terapia , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
OBJECTIVE: To explore the mechanism of electroacupunctureï¼EAï¼ in improving learning-memory ability in Alzheimer's disease ï¼ADï¼ mice from the perspective of endosomal-lysosomal system. METHODS: Male APP/PS1 transgenic mice were randomly divided into model group and EA group ï¼n=10 in each groupï¼ and 10 male C57BL/6 wild mice were taken as the normal group. EA ï¼1 Hz/50 Hz, 1 mAï¼ was applied at bilateral "Yongquan"ï¼KI1ï¼ and acupuncture was applied at "Baihui" ï¼GV20ï¼ for 15 min. The mice of the model and normal groups were subjected to restriction with the same method as those of the EA group for 15 min. The treatment was conducted once every other day for 6 weeks. The spatial learning-memory ability ï¼shown by escape latency of place navigation test and the time of crossing the target platform and total swimming distance in the target quadrant in 1 min of spatial probe test ï¼ was detected by Morris water maze test. The immunoactivity of senile plaques ï¼SPï¼ in the hippocampus tissue was detected by immunohistochemistry. The ultrastructural characters of hippocampal neurons were observed by transmission electron microscope, and the expression levels of Ras-related protein 5 ï¼Rab5ï¼, Ras-related protein 7 ï¼Rab7ï¼ and cathepsin D ï¼CTSDï¼ in the hippocampus were detected by Western blot, separately. RESULTS: Compared with the normal group, the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD were significantly increased ï¼P<0.05, P<0.01ï¼, while the number of crossing the original platform and the total swimming distance in the platform quadrant were considerably reduced ï¼P<0.05ï¼ in the model group. In contrast to the model group, the EA group had a marked decrease in the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD ï¼P<0.05, P<0.01ï¼, and a striking increase in the number of crossing the original platform and the swimming distance in the platform quadrant ï¼P<0.05ï¼. Results of transmission electron microscope showed an accumulation of endosome, lysosome, and endolysosomes in the hippocampal neurons in the model group, which was evidently milder in the EA group. CONCLUSION: EA of GV20 and KI1 can improve the learning-memory ability of AD mice, which may be related to its function in reducing hippocampal Aß deposition and down-regulating endosomal-lysosomal system activity.
Asunto(s)
Enfermedad de Alzheimer , Electroacupuntura , Masculino , Ratones , Animales , Ratones Endogámicos C57BL , Ratones Transgénicos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Endosomas , Lisosomas/genética , Placa AmiloideRESUMEN
OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of ß-amyloid (Aß) and autophagy-related proteins in hippocampal cells of Alzheimer's disease (AD) model mice, so as to explore its underlying mechanisms. METHODS: Eighteen male APP/PS1 transgenic mice (6 months old) were randomly divided into model and EA groups, with 9 mice in each group. Nine male C57BL/6 wild-type mice of the same age were chosen as the normal group. Mice in the EA group were treated with acupuncture on "Baihui" (GV20) and EA (1 Hz/50 Hz, 1 mA) on bilateral "Yongquan" (KI1), once every other day, 20 min each time for a total of 21 times. After the interventions, the spatial learning and memory ability were observed by Morris water maze test. The autophagy-related pathological changes in hippocampus were observed by transmission electron microscopy. The expressions of microtublue associated protein 1 light chain 3 (LC3) and Aß in hippocampus were observed by immunofluorescence and the expression levels of LC3 and p62 proteins were detected by Western blot. RESULTS: Compared with the normal group, the escape latency was prolonged (P<0.01), the residence time in the original quadrant platform was shor-tened (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3â ¡ and p62 proteins, and the ratio of LC3â ¡/LC3â proteins in hippocampus were increased (P<0.01, P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05), the residence time in the original quadrant platform was prolonged (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3â ¡ and p62 proteins, and the ratio of LC3â ¡/LC3â proteins in hippocampus were decreased (P<0.05) in the EA group. The transmission electron microscopy showed that the structure of neurons was normal in the normal group, a large number of autolysosomes and autophagosomes existed in hip-pocampal nerve cells in the model group, and only a small number of autophagosomes were observed in the EA group. CONCLUSION: EA can reduce the expression levels of autophagy-related proteins LC3 and p62 in APP/PS1 transgenic mice, improve the hip-pocampal autophagy state, reduce intracellular Aß aggregation, and thus improve the learning and memory ability.