Pereira, V. S. | Search bioRxiv

bioRxiv2017

An eutherian intronic sequence gave rise to a major satellite DNA in Platyrrhini

Satellite DNAs (satDNAs) are major components of eukaryote genomes. However, because of their quick divergence, the evolutionary origin of a given satDNA family can rarely be determined. Herein we took advantage of available primate sequenced genomes to determine the origin of the CapA satDNA (~1,500 bp long monomers), first described in Sapajus apella. We show that CapA is an abundant satDNA in Platyrrhini, whereas in the genomes of most eutherian mammals, including humans, this sequence is present only as a single copy located within a large intron of the NOS1AP (nitric oxid synthase 1 adaptor protein) Gene. Our data suggest that this intronic CapA-like sequence gave rise to the CapA satDNA and we discuss possible mechanisms implicated in this event. This is the first report of a single copy intronic sequence giving origin to a satDNA that reaches up to 100,000 copies in some genomes.

genomics↗

bioRxiv2016

Antidepressant-like effects of P2 purinergic antagonist PPADS is dependent on serotonergic and noradrenergic integrity

Depression is a common mental disorder affecting around 350 million of individuals globally. The available antidepressant drug monotherapy is far from ideal since it has an efficiency of approximately 60% and takes around 3-4 week to achieve clinical improvement. Attention has been paid to the purinergic signaling regarding neuropathological mechanisms, since it might be involved in psychiatric disorders, such as depression. In fact, blockade of purinergic P2X receptors induces antidepressant-like effects in preclinical models. However, the mechanisms involved in this effect are not yet completely understood. The present work investigated the interplay between a P2X receptor antagonist (PPADS) and clinically used antidepressant drugs on the forced swimming test, an animal model predictive of antidepressant effect. We observed significant synergistic effect of PPADS combined with sub-effective doses of fluoxetine or reboxetine in the FST. Moreover, depletion of serotonergic or noradrenergic systems, with PCPA and DSP-4 treatment, respectively, blocked the antidepressant-like effect of PPADS. No increase in locomotion, a possible source of confusion on FST data, was detected in any of the treated groups. Our results indicate the antidepressant-like effect of PPADS depends on the integrity of serotonergic and noradrenergic transmission.

pharmacology and toxicology↗