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The interaction between Nitric Oxide Synthase related short and long non-coding RNAs in thecontext of memory formation, aging and neurogenesis
Nitric Oxide Synthase (NOS) is an enzymatic catalyst responsible for producing Nitric Oxide (NO), a signalling molecule involved in many physiological and pathological processes. For such processes, which include memory formation and neurogenesis, the timing and scale of NO production is critical. The activity and availability of NOSs must therefore be tightly regulated. The majority of this thesis focuses on the role of two non-coding RNAs (ncRNAs) in NOS regulation: a microRNA and a long, cis-encoded natural antisense transcript (NAT). Of particular interest is how these ncRNAs interact to regulate NO production during memory formation, aging, and neurogenesis. This was primarily investigated in Lymnaea stagnalis, an animal model with a well-defined central nervous system and neuronal network underlying NO-dependent memory formation. An orthologous NAT was also analysed in the mouse brain, building upon past research to further investigate which neurological processes the RNA maybe implicated in.First, the results of this thesis demonstrate that a NOS-related, long NAT is functionally targeted by a microRNA. Second, results show that both ncRNAs are differentially regulated in a key area of the Lymnaea brain after training, and that this correlates with previously established critical time windows for successful memory formation. Third, the results show that the ncRNAs are differentially expressed in the Lymnaea brain throughout aging, providing evidence for a contribution to the molecular basis of age-related memory decline. Fourth, the results of mouse brain ISH will demonstrate that the mammalian NOS-related NAT ortholog is co-expressed with its regulatory target in various regions of functional importance.</p
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Research data for paper 'Time dependent differential regulation of a novel long non-coding natural antisense RNA during long-term memory formation'.
Behavioural data used in paper published in Scientific ReportsDataset for Fig. 4a: The results of the behavioural test of long-term memory (LTM) formation at 24 h after single-trial food reward classical conditioning. The data shown are difference scores calculated by subtracting the number of spontaneous feeding rasps counted in a two-minute period before the application of the conditioned stimulus from those counted in the two-minute period after the conditioned stimulus was applied.AbstractLong natural antisense transcripts (NATs) have been demonstrated in significant numbers in a variety of eukaryotic organisms. They are particularly prevalent in the nervous system suggesting their importance in neural functions. However, the precise physiological roles of the overwhelming majority of long NATs remain unclear. Here we report on the characterization of a novel molluscan nitric oxide synthase (NOS)-related long non-coding NAT (Lym-NOS1AS). This NAT is spliced and polyadenylated and is transcribed from the non-template strand of the Lym-NOS1 gene. We demonstrate that the Lym-NOS1AS is co-expressed with the sense Lym-NOS1 mRNA in a key neuron of memory network. Also, we report that the Lym-NOS1AS is spatially and temporally regulated by one-trial conditioning leading to long-term memory (LTM) formation. Specifically, in the cerebral, but not in the buccal ganglia, the temporal pattern of changes in Lym-NOS1AS expression after training correlates well with the alternation of memory lapse and non-lapse periods. Our data suggest that the Lym-NOS1AS plays a role in the consolidation of nitric oxide-dependent LTM.</p