Neuroscience
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Binge eating disorder is the most prevalent eating disorder, affecting both sexes but more commonly found in women. Given the frequent co-occurrence of psychiatric disorders, this study aimed to establish a standardized experimental intermittent protocol to investigate overeating associated with depression. A 10-day protocol induced uncontrolled eating behavior in C57BL/6J female mice. ⋯ Moreover, both fasting sucrose groups exhibited elevated corticosterone levels. In a separate design (Experiment 2), groups with 16 and 20 h of fasting alone (without sucrose) did not show the same behavioral results as the intermittent fasting sucrose groups, thus avoiding fasting bias. Based on these results, the 20-hour sucrose fasting group was chosen as the ideal protocol for mimicking overeating behavior associated with depression to investigate future therapeutic approaches for this comorbidity.
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HECT domain and Ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) is an E3 ubiquitin ligase involving oxidative stress, an important contributor in cerebral ischemia-reperfusion injury (CIRI). It was proposed to be associated with the PI3K/AKT pathway and Nrf2 nuclear translocation, which are important players of oxidative stress. Therefore, we supposed that HACE1 might affect CIRI by regulating the PI3K/AKT/Nrf2 pathway. ⋯ Similarly, HACE1 overexpression inhibited neuronal apoptosis caused by OGD/R treatment. The PI3K inhibitor LY294002 reversed the inhibitory effects of HACE1 overexpression on oxidative stress in OGD/R-injured cells, accompanied by the inactivated AKT/Nrf2 pathway. Altogether, our results suggest that HACE1 protects against oxidative stress-induced neuronal apoptosis in CIRI by activating the PI3K/AKT/Nrf2 pathway, providing a new insight into the CIRI treatment.
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Alzheimer's disease (AD) is the most common cause of dementia and is caused by various factors including amyloid-beta (Aβ) aggregation. We investigated the pharmacological effects of the ethanol extract of Potentilla fragarioides var. major (Rosaceae) (EEPF) on AD-related pathogenesis, which remain elusive. We observed the effects of EEPF on Aβ disaggregation and free-radical scavenging activities for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) using in vitro assays, evaluated the effects of EEPF on memory loss in two animal models, and examined the molecular regulatory mechanisms of EEPF using an antibody-protein microarray in EEPF-treated neuronal cell lines. ⋯ In lipopolysaccharide (LPS)-stimulated BV-2 microglia, EEPF significantly inhibited LPS-induced production of inflammatory factors, such as nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-6, and decreased the phosphorylation of Smad3 and cyclin D3. High-performance liquid chromatography confirmed that EEPF has five major components: neochlorogenic acid, chlorogenic acid, polydatin, isochlorogenic acid A, and buddleoside, with amounts ranging across 1.91-9.41 mg/g. EEPF may be a promising drug for treatment of AD and AD-related brain disorders.
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Respiratory muscle paralysis due to trauma or neurodegenerative diseases can have devastating consequences. Only a few studies have investigated the reconstruction of motor function in denervated diaphragms caused by such conditions. Here, we studied the efficacy of transplanting E14 embryonic spinal motor neurons (SMNs) into peripheral nerve grafts for functionally reconstructing a denervated diaphragm in a rat model. ⋯ The SMNs transplanted into the peripheral nerve grafts formed a structure similar to the spinal cord, and the neuromuscular junction of the denervated diaphragm was reinnervated. These findings suggest the establishment of an ectopic motor neuron pool in the peripheral nerve graft. Free peripheral intra-nerve SMN transplantation in combination with NMES, which can be applied for diaphragmatic pacing, offers novel insights into the development of neuroregenerative therapies for treating life-threatening and intractable respiratory muscle paralysis caused by severe nerve damage and degenerative diseases.