Mitochondrial dysfunction has been repeatedly identified to be hallmark brain pathology underlying neuronal stress in Alzheimer’s disease. As a result, mitochondrial medicine for the treatment of Alzheimer’s disease has received increasing recognition. Idebenone (IDB) is a synthetic analog of Coenzyme Q10 (CoQ10) carrying antioxidizing property. Previous clinical trials reported a conflicting disease-modifying effect of IDB on Alzheimer’s disease patients. However, whether IDB is preventive against amyloid beta (Aβ)-induced mitochondrial and neuronal stress has not been comprehensively investigated. In this study, we adopted an in-vitro setting by using primary cultured cortical neurons for the test. Neurons were pretreated with IDB prior to Aβ exposure. IDB pretreatment significant prevented neurons from Aβ-induced collapse of mitochondrial bioenergetics and perturbations of the protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling. Importantly, the treatment of IDB alone demonstrated an indiscernible side effect on the measured mitochondrial function, PKA/CREB signaling and neuronal viability. Therefore, our findings in together show a preventive effect of IDB against Aβ-mediated mitochondrial and neuronal injury. The use of IDB may hold potential to reduce the risk of Alzheimer’s disease as a preventive strategy.
Acupuncture is widely used to treat various neurodegenerative diseases and can effectively improve cognitive and memory states in Alzheimer’s disease. However, its mechanism is unclear. We speculated that the effect of acupuncture on cognitive function may be associated with reductions in the levels of Aβ and phosphorylated tau in the brain. In this experiment, 60 male Sprague–Dawley rats were randomly divided into control, model, electroacupuncture and nonacupoint groups. We perform electroacupuncture at Shenting (GV24) and bilateral Benshen (GB13) acupoints once a day for 4 weeks in electroacupuncture group (with 1 day of rest after every 6 days of treatment). The electroacupuncture group showed a better performance in cognitive-related behavior tests and significantly lowers the levels of Aβ, p-tau (s396) and p-tau (s404) in the hippocampus. These results may suggest that electroacupuncture at the GV24 and bilateral GB13 acupoints might improve cognitive functions in Alzheimer’s disease by decreasing the levels of Aβ, p-tau (s396) and p-tau (s404) in the brain as these proteins are the main causes of neurological damage and cognitive dysfunction during the pathogenesis underlying Alzheimer’s disease.
Eriodictyol, a natural flavonoid compound identified in numerous medicinal plants, has been reported to have anti-inflammatory, antioxidative and antiproliferative activities and exert protective effects on the neurons, thus drawing attention to its therapeutic potential. However, the effect of eriodictyol on depression remains unclear. In the present study, we investigated the behavioral effects of chronic eriodictyol treatment in rat models of depression induced by lipopolysaccharide (LPS, 1 mg/kg) challenge and chronic unpredictable mild stress (CUMS). We found that chronic eriodictyol (10, 30, and 100 mg/kg) treatment by oral gavage once daily for 14 days dose-dependently produced antidepressant effect in the forced swim test (FST), but did not alter locomotor activity in the open field test. Moreover, oral administration with eriodictyol (100 mg/kg) for 28 days reversed the depressive- and anxiety-like behaviors induced by LPS or CUMS, as evidenced by significantly increased sucrose preference in the sucrose preference test, reduced immobility time in the FST, and reduced latency to feeding in the novelty-suppressed feeding test. In addition, co-administration of subthreshold doses of eriodictyol (30 mg/kg) and transient potential vanilloid 1 receptor antagonist capsazepine (1.5 mg/kg) produced a synergistic effect in these tests. Chronic eriodictyol administration at a dose of 100 mg/kg also rescued the memory deficits induced by CUMS as indicated by the increased exploration index in the novel object recognition test. Altogether, these results demonstrate that eriodictyol attenuates depressive- and anxiety-like behaviors and cognitive impairments in rats, and might be a potential therapeutic avenue for depression.
Melanocortins are neuropeptides exerting versatile functions in the nervous system. Melanocortin 4 receptor (MC4R) is primarily expressed in the brain and is thought to be a major mediator for melanocortin. Brain-derived neurotrophic factor (BDNF) may be a crucial downstream molecule of MC4R activation, to yield neurite outgrowth, neuroregenerative, anorexigenic and other actions. In this study, we stimulated Neuro2a murine neuronal cells with an α-melanocyte stimulating hormone (α-MSH) analog, [Nle(4), D-Phe(7)]melanocyte-stimulating hormone (NDP-MSH). In Neuro2a cells, NDP-MSH promoted neurite outgrowth. Upon NDP-MSH administration, BDNF expression was greatly enhanced. Furthermore, this effect was effectively reversed by the MC4R antagonist, JKC-363. We found that NDP-MSH treatment activated the ERK cascade and its downstream kinase MSK1 (mitogen- and stress-activated protein kinase-1). Antagonism of the MSK1 cascade by a specific inhibitor or overexpression of a defective MSK1 mutant interrupted the phosphorylation of the transcription factor cAMP-response element binding protein (CREB), blocking BDNF upregulation. In addition, MSK1 activation triggered an epigenetic alteration in histone H3 (Ser10), facilitating the expression of the BDNF gene. Taken together, our results showed that MSK1 kinase positively activates MC4R-induced BDNF expression via modulating the phosphorylation of CREB and histone H3 in Neuro2a neuronal cells.
With an increase in the number of spinal cord injuries (SCIs) in China, severe dysfunction of the limb below the injured segment is prominent. Among the studies centered on the factors inducing SCIs, inflammatory response has a dramatic input on the pathogenesis of SCIs.
This study aimed to investigate the effects of Tricholoma matsutake polysaccharides (TMP) on function recovery following SCIs.
The cell viability, neurite growth, NF-kappa B, TNFα and IL-6 production from hydrogen peroxide-treated PC12 cells were analyzed. In-vivo, a total of 36 male C57 mice were divided into sham group, SCI group and TMP group (100 mg/kg). The protective effects of TMP were evaluated by Basso mouse scale (BMS) scores, HE staining, immunofluorescence and Western blotting.
TMP promoted neurite growth and inhibited TNFα, IL-6 and NF-kappa B signaling in a concentration-dependent manner in vitro. Moreover, compared with the SCI group, the BMS scores and nerve regeneration showed a significant increase, while NF-kappa B signaling, TNFα and IL-6 production significantly decreased after TMP treatment.
TMP has a protective effect against SCIs in vitro and in vivo, which may be a potential strategy for future application in clinical practice.
A recent study showed that objects’ roughness (smooth or rough) was held in visual working memory (VWM) in the ventral visual cortex and the intraparietal sulcus (IPS). Here, we investigated the functional differences between these areas in the context of VWM of material properties. We focused on the process in which participants accurately extracted and maintained in their memories the glossiness and roughness of a sphere. Human participants performed two types of delayed material (glossiness or roughness) discrimination tasks in which they judged which task was to be performed based on the differences in the material properties of two sequentially presented sample spheres. This task allowed us to investigate how the visual system in the human brain could properly extract a material property and hold the information in VWM. By decoding the task information (glossiness or roughness) from the brain activity patterns in the delay period, we found that both the ventral visual cortex and the IPS contributed to maintenance in memory of material properties. We also showed different decoding patterns in the areas over the course of each trial; the ventral visual cortex performed at levels above chance performance in extracting a material property, and the IPS performed at levels above chance performance in maintaining the property in memory. These results suggest that, in VWM, material properties are visually processed in the ventral visual cortex, and the visual information is sent to the IPS to be robustly maintained.