Neuroscience
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Status epilepticus (SE) is a life-threatening condition needing immediate care to prevent brain damage. SE with electrographic and behavioral features similar to those seen in humans is reproduced in rodents by i.p. pilocarpine injection, and can be terminated by diazepam and ketamine treatment but only behaviourally, not electrographically. Little is known on the behavioral and EEG effects induced by a delayed administration of ketamine (25 mg/kg) after diazepam (10 mg/kg) or vice versa. ⋯ However, diazepam administration before ketamine significantly shortened the time of behavioral recovery compared to when ketamine was administered before diazepam (p < 0.05). The two protocols were also associated to distinct EEG changes in gamma and high frequency oscillations. In conclusion, although diazepam and ketamine are not effective in stopping EEG SE, diazepam administration one hour before ketamine shortens behavioral recovery in pilocarpine-treated mice.
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SNARE-complexes drive the fusion of membrane-bound vesicles with target membranes or with each other (homotypic fusion). The SNARE-proteins are subdivided into Qa, Qb, Qc and R-SNAREs depending on their position in the four-helical SNARE-bundle. Here, we review the SNAP-25 protein sub-family, which includes both the Qb and Qc SNARE-domains within a single protein. ⋯ SNAP-29 is present on intracellular membranes and performs functions in autophagosome-to-lysosome fusion, among others. An overlapping function for SNAP-47 was described; in addition, SNAP-47 mediates postsynaptic AMPA-receptor insertion. Overall, the presence of two SNARE-domains confers members of this family the ability to associate to different Qa and R-SNAREs and drive diverse membrane fusion reactions; one member of the family, SNAP-25, has been devoted entirely to Ca2+-triggered fusion and has taken on a number of additional, regulatory roles.
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In central synapses, synaptobrevin-2 (also called VAMP-2) is the predominant synaptic vesicle SNARE protein that interacts with the plasma membrane SNAREs, SNAP-25 and syntaxin-1 to execute exocytosis. Mice deficient in synaptobrevin-2 or SNAP-25 show embryonic lethality, which precludes investigation of the complete loss-of-function of these proteins in the adult nervous system. However, mice that carry heterozygous null mutations survive into adulthood and are fertile. ⋯ This analysis revealed only mild phenotypes, SNAP-25 (+/-) mice exhibited marked hypoactivity, whereas synaptobrevin-2 (+/-) mice showed enhanced performance on the rotarod. The two mouse lines did not manifest significant deficits in anxiety-related behaviors, learning and memory measures, or prepulse inhibition. The rather mild behavioral deficits indicate that these key proteins, SNAP25 and synaptobrevin-2, are expressed in excess to circumvent the impact of potential fluctuations in expression levels on nervous system function.
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Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins mediate membrane fusion events in eukaryotic cells. Traditionally recognized as major players in regulating presynaptic neurotransmitter release, accumulative evidence over recent years has identified several SNARE proteins implicated in important postsynaptic processes such as neurotransmitter receptor trafficking and synaptic plasticity. Here we analyze the emerging data revealing this novel functional dimension for SNAREs with a focus on the molecular specialization of vesicular recycling and fusion in dendrites compared to those at axon terminals and its impact in synaptic transmission and plasticity.