Neuroscience
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Brain edema is an important complication of acute hepatic encephalopathy (AHE), and astrocyte swelling is largely responsible for its development. Elevated blood and brain ammonia levels have been considered as major etiological factors in this edema. In addition to ammonia, recent studies have suggested that systemic infection, inflammation (and associated cytokines (CKs)), as well as endotoxin (lipopolysaccharide (LPS)) are also involved in AHE-associated brain edema. ⋯ CM derived from ECs treated with ammonia, along with antioxidants (AOs) or the NF-κB inhibitor BAY 11-7082, when added to astrocytes resulted in a significant reduction in cell swelling, as compared to the effect of CM from ECs-treated only with ammonia. We also identified increased nuclear NF-κB expression in rat brain cortical ECs in the thioacetamide (TAA) model of AHE. These studies suggest that ECs significantly contribute to the astrocyte swelling/brain edema in AHE, likely as a consequence of oxidative/nitrative stress and activation of NF-κB.
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The hippocampus is required for short-term memory and contains both excitatory pyramidal cells and inhibitory interneurons. These cells exhibit various forms of synaptic plasticity, the mechanism underlying learning and memory. More recently, endocannabinoids were identified to be involved in synaptic plasticity. ⋯ We observed that the expression of endocannabinoid biosynthetic enzyme mRNA does occur within interneurons and that it is coexpressed with type I metabotropic glutamate receptors, suggesting interneurons have the potential to produce endocannabinoids. We also identified that CA3 and CA1 pyramidal cells express endocannabinoid biosynthetic enzyme mRNA. Our data provide the first molecular biological evidence for putative endocannabinoid production in interneurons, suggesting their potential ability to regulate endocannabinoid-mediated processes, such as synaptic plasticity.
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Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian brain. This peptide regulates many physiological functions and behaviors, such as cardio-respiratory control, thermoregulation, nociception, feeding, memory processes and motivational responses, and plays a prominent role in emotional responses including anxiety and depression. CCK-expressing brain regions involved in these functions remain unclear and their identification represents an important step towards understanding CCK function in the brain. ⋯ This procedure efficiently reduced CCK levels locally. shCCK-treated animals showed reduced levels of anxiety in the elevated plus-maze, and lower despair-like behavior in the forced swim test. Our data demonstrate that CCK expressed in the BLA represents a key brain substrate for anxiogenic and depressant effects of the peptide. The study also suggests that elevated amygdalar CCK could contribute to panic and major depressive disorders that have been associated with CCK dysfunction in humans.
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In teleost fish, sex differences in several behavioral and physiological traits have been assumed to reflect underlying sex differences in the central expression of neurotransmitter/neuromodulator-related molecules, including vasotocin (VT)/isotocin (IT), gonadotropin-releasing hormone (GnRH), and tyrosine and tryptophan hydroxylases (TH and TPH). However, the sex-dependent expression patterns of these molecules have not been fully characterized in the teleost brain. In the present study, we therefore systematically evaluated sex differences in their expression in the medaka (Oryzias latipes) brain. ⋯ In contrast, the overall expression levels of it and gnrh3 were higher in the female brain than in the male brain. Equally importantly, no conspicuous sex differences were observed in the expression of gnrh2, th1, and th2, despite several previous reports of their sex-biased expression in the brains of other teleost species. Taken together, these data have uncovered previously unidentified sex differences in the expression of VT/IT, GnRH, and TPH in the teleost brain, which may possibly be relevant to sexual dimorphism in some behavioral and/or physiological traits, and have simultaneously highlighted potential species differences in the roles of these molecules.
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Synaptotagmin (syt) I is a Ca(2+) sensor that has been thought to trigger all vesicle secretion with similar mechanisms. However, given the calcium and stimulation requirements of small clear, and large dense core vesicles, we hypothesized that syt I expression differentially regulates vesicle release. Therefore, in this study, we generated multiple stable cell lines of PC12 cells that each had a different and stable level of syt I expression. ⋯ We used an immunoassay to measure NPY release and found that NPY release was abolished in cells that had abolished syt I expression, but cell lines that expressed 50-60% of control levels of syt I exhibited NPY release levels comparable to release of NPY from control cells. Furthermore, the vesicle fusion pore exhibited a reduced open duration when syt I was abolished, but a longer open duration time for 50% syt I expression than control cells. Therefore, vesicles have a threshold for syt I that is required to control opening of the fusion pore, expansion, and full fusion to release large dense core proteins, but not for full fusion of the small molecules like NE.