Biology subjects

Guimaraes, F. S.

Publications and source records attributed to Guimaraes, F. S..

3 recordsLinked to original sources

bioRxiv2018

Activation of the TRKB receptor mediates the panicolytic-like effect of NOS inhibitor aminoguanidine

Nitric oxide (NO) triggers escape reactions in the dorsal periaqueductal gray matter (dPAG), a core structure mediating panic-associated responses, and decreases the release of BDNF in vitro. BDNF mediates the panicolytic effect induced by antidepressant drugs and produces these effects per se when injected into the dPAG. Based on these findings, we hypothesize that nitric oxide synthase (NOS) inhibitors would have panicolytic properties associated with increased BDNF signaling in the dPAG. We observed that the repeated (7 days), but not acute (1day), systemic administration of the NOS inhibitor aminoguanidine (AMG; 15 mg/kg/day) increased the latency to escape from the open arm of the elevated T-maze (ETM) and inhibited the number of jumps in hypoxia-induced escape reaction in rats, suggesting a panicolytic-like effect. Repeated, but not acute, AMG administration (15mg/kg) also decreased nitrite levels and increased TRKB phosphorylation at residues Y706/7 in the dPAG. Notwithstanding the lack of AMG effect on total BDNF levels in that structure, the microinjection of the TRK antagonist K252a into the dPAG blocked the anti-escape effect of this drug in the ETM. Taken together our data suggest that the inhibition of NO production by AMG increased the levels of pTRKB, which is required for the panicolytic-like effect observed.

neuroscience↗

bioRxiv2017

Elastase-2 knockout mice display anxiogenic- and antidepressant-like phenotype: putative role for BDNF metabolism in prefrontal cortex

Several pieces of evidence indicate that elastase-2 (ELA2; chymotrypsin-like ELA2) is an alternative pathway to the generation of angiotensin II (ANG II). Elastase-2 knockout mice (ELA2KO) exhibit alterations in the arterial blood pressure and heart rate. However, there is no data on the behavioral consequences of ELA2 deletion. In this study we addressed this question, submitting ELA2KO and wild-type (WT) mice to several models sensitive to anxiety- and depression-like, memory, and repetitive behaviors. Our data indicates a higher incidence of barbering behavior in ELA2KO compared to WT, as well as an anxiogenic phenotype, evaluated in the elevated plus maze (EPM). While a decrease in locomotor activity was observed in ELA2KO in EPM, this feature was not the main source of variation in the other parameters analyzed. The marble burying test (MBT) indicated increase in repetitive behavior, observed by a higher number of buried marbles. The actimeter test indicated a decrease in total activity and confirmed the increase in repetitive behavior. The spatial memory was tested by repeated exposure to the actimeter in a 24h interval. Both ELA2KO and WT exhibited decreased activity compared to the first exposure, without any distinction between the genotypes. However, when submitted to the cued fear conditioning, ELA2KO displayed lower levels of freezing behavior in the extinction session when compared to WT, but no difference was observed during the conditioning phase. Increased levels of BDNF were found in the prefrontal cortex but not in the hippocampus of ELA2KO mice compared to WT. Finally, in silico analysis indicates that ELA2 is putatively able to cleave BDNF, and incubation of the purified enzyme with BDNF led to the degradation of the later. Our data suggested an anxiogenic- and antidepressant-like phenotype of ELA2KO, possibly associated with increased levels of BDNF in the prefrontal cortex.

animal behavior and cognition↗

bioRxiv2016

Inducible nitric oxide synthase (NOS2) knockout mice as a model of trichotillomania

Trichotillomania (TTM) is an impulse control disorder characterized by repetitive hair pulling/trimming. Barbering behavior (BB) has been observed in laboratory animals and proposed as TTM model. The neurobiological basis of TTM is not clear, but it seems to involve striatal hyperactivity parallel to hypoactivation of prefrontal cortex. In this study we observed that knockout mice to the inducible isoform of nitric oxide synthase (NOS2) exhibit exacerbated BB following the 4th week of age, as well as increased repetitive movements compared to wild-type mice (WT). These behaviors are associated to decreased levels of NMDA receptor subunit (NR1) in prefrontal cortex, while an increase was observed in striatum of NOS2KO compared to WT. Striatal neurons from NOS2KO also exhibited increased number of branches compared to WT. The repeated treatment with clomipramine, a clinically approved drug to treat TTM in humans, or memantine, an antagonist of NMDA receptors, as well as partial rescue of NOS2 expression in haploinsufficient animals, attenuated the expression of BB. The silencing of NOS2 expression reduced the MAP2 (microtubule-associated protein 2) levels in activity-induced differentiated PC12 cells. Our data led us to propose that NOS2 regulates the neuronal maturation of the inhibitory afferent pathways to striatum during neurodevelopment, and such inadequate inhibition of striatal motor programs might be associated to the observed phenotype.

animal behavior and cognition↗