Neuroscience
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Activation of P2X7 receptor (P2X7R), a purinergic receptor, expressed by neurons is well-known to induce their death, but whether or not their sensitivity to ATP depends on its expression levels remains unclear. Here, we examined the effect of the expression level of P2X7Rs on cell viability using pure neuron cultures, co-cultures with astrocytes derived from SJL- and ddY-strain mice, and mouse P2X7R-expressing HEK293T cell systems. Treatment of pure neuron cultures with 5mM ATP for 2h, followed by 3-h incubation in fresh medium, resulted in death of both types of neurons, and their death was prevented by administration of P2X7R-specific antagonists. ⋯ The ATP-induced neuronal death was greater for SJL-neurons than for ddY-ones, this being correlated with the expression level of P2X7R in them, and the same results were obtained for the HEK293T cell systems. Co-culture of neurons with astrocytes increased the ATP-induced neuronal death compared to the case of pure neuron cultures. Overall, we reveal that neuronal vulnerability to ATP depends on the expression level of P2X7R, and co-existence of astrocytes exacerbates ATP-induced neuronal death.
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Microglia have multiple functions in regulating homeostasis in the central nervous system (CNS), and microglial inflammation is thought to play a role in the etiology of the neurodegenerative diseases. When endogenous or exogenous stimuli trigger disorders in microenvironmental homeostasis in CNS, microglia critically determine the fate of other neural cells. ⋯ Though the interaction between autophagy and macrophages has been reported and reviewed in length, the role of autophagy in microglia has yet to be reviewed. Herein, we will highlight recent advances on the emerging role of autophagy in microglia, focusing on the regulation of autophagy during microglial inflammation, and the possible mechanism involved.
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Binge eating is defined by the consumption of an excessive amount of food in a short time, reflecting a form of hedonic eating that is not necessarily motivated by caloric need. Foods consumed during a binge are also often high in fat and/or sugar. Ghrelin, signaling centrally via the growth-hormone secretagogue receptor (GHSR), stimulates growth hormone release and appetite. ⋯ GHSR KO mice also had reduced activation of the nucleus accumbens shell, but not core, following HFD consumption. These data support the ability of INT HFD in mice to induce a binge-compensate pattern of intake that emulates select components of binge eating in humans. There also appears to be a role for GHSR signaling in driving HFD consumption under these conditions, potentially via mediation of reward-related circuitry.
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The aim of this study was to investigate the role of monoamine neurotransmitters on the severity of experimental autoimmune encephalomyelitis (EAE) in obese mice. EAE was induced in mice with normal diets (ND-EAE) and obese mice with high-fat diets (HFD-EAE) through the immune response to myelin oligodendrocyte glycoprotein (MOG) (35-55). The levels of dopamine (DA), serotonin (5-HT) and their metabolites in different anatomical brain regions were measured by high-performance liquid chromatography. ⋯ The cytokine levels in the plasma, tissues, and cultured splenocytes were found to be significantly altered in EAE mice compared with control mice. Moreover, HFD-EAE mice exhibited significantly higher MMP-9 activity and lower IL-4 levels than ND-EAE mice and were significantly correlated with brain 5-HT levels. In conclusion, the increased 5-HT levels in the brain significantly correlated with MMP-9 activity and IL-4 levels play an important role in the exacerbation of disease severity in HFD-EAE mice.
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Long noncoding RNAs (lncRNAs) are abundant in the central nervous system and have a key role in brain function as well as many neurological disorders. However, the regulatory function of lncRNAs in the premature brain has not been well studied. This study described the expression profile of lncRNAs in premature mice using microarray technology. 1999 differentially expressed lncRNAs and 955 differentially expressed mRNAs were identified. ⋯ Additionally, the lncRNA-mRNA-network and TF-gene-lncRNA-network were constructed to identify core regulatory lncRNAs and transcription factors. The sex-determining region of Y chromosome (SRY) gene may be a key transcription factor that regulates premature brain development and injury. This study for the first time represents an expression profile of differentially expressed lncRNAs in the premature brain and may provide a novel point of view into the mechanisms of premature brain injury.