ABSTRACT
Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer's disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes; these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer's disease. Our literature search found that phenotypic changes occur continuously in Alzheimer's disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer's disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer's disease.
ABSTRACT
OBJECTIVE: To observe the effect of acupuncture and moxibustion on the water content of stratum corneum (WCSC), expression of serum inflammatory factors and aquaporin 3 (AQP3) in skin, lung and rectum in guinea pigs with eczema of skin damp-heat accumulation, and to explore the possible mechanism of acupuncture and moxibustion for regulating skin barrier function. METHODS: A total of 24 male albino guinea pigs were randomly divided into a blank group (n=6) and a modeling group (n=18). The guinea pigs in the modeling group were induced by 2,4-dinitrochlorobenzene (DNCB) to establish the eczema model of skin damp-heat accumulation. The guinea pigs with successful modeling were further randomly divided into a model group, a medication group and an acupuncture-moxibustion group, 6 guinea pigs in each group. The guinea pigs in the medication group were treated with loratadine tablets (0.8 mg/kg) by gavage, once a day for 7 days; the guinea pigs in the acupuncture-moxibustion group were treated with acupuncture at "Feishu" (BL 13), "Pishu" (BL 20), "Quchi" (LI 11), "Zusanli" (ST 36) and "Xuehai" (SP 10); at the same time, moxibustion was applied at "Feishu" (BL 13) and "Zusanli" (ST 36), moxibustion intervention for 10 min and needle retaining for 15 min at each acupoint, once a day for 7 days. The eczema area and severity index (EASI) score was evaluated before and After intervention, and WCSC and trans-epidermal water loss (TEWL) were measured by skin tester. After intervention, The HE staining was used to observe the changes of skin histomorphology in each group; ELISA was used to measure the contents of serum immunoglobulin E (IgE), interleukin (IL)-4 and IL-17; Western blot was used to measure the protein expression of AQP3 in skin, lung and rectum. RESULTS: Before the intervention, compared with the blank group, the EASI scores and TEWL were increased in the remaining groups (P<0.01), and the WCSC was decreased (P<0.01). After the intervention, compared with the model group, the EASI scores and TEWL were decreased (P<0.05, P<0.01), and WCSC was increased (P<0.01) in the medication group and the acupuncture-moxibustion group. The epidermal structure in the blank group was complete and the fibers in the dermis were arranged orderly; in the model group, epidermal hyperkeratosis, proliferation of granular layer, spinous cell layer and basal layer, and disordered arrangement of dermal fibers and infiltration of inflammatory cells were observed. The morphological performance in the medication group and the acupuncture-moxibustion group was better than that in the model group. Compared with the blank group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 and the protein expression of AQP3 in skin, lung and rectum were decreased in the model group (P<0.01, P<0.05). Compared with the model group, the contents of serum IgE and IL-17 were decreased and the contents of serum IL-4 were increased in the medication group and the acupuncture-moxibustion group (P<0.01), and the protein expression of AQP3 in skin, lung and rectum in the acupuncture- moxibustion group were increased (P<0.05). Compared with the medication group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 was decreased (P<0.01) in the acupuncture-moxibustion group. CONCLUSION: Acupuncture and moxibustion could improve the epidermal water metabolism and skin tissue morphology in guinea pigs with eczema of skin damp-heat accumulation. Its mechanism may be related to regulating inflammatory factors, up-regulating the expression of AQP3, and then repairing the skin barrier function.
