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.