Biology subjects

Rocha, S. P.

Publications and source records attributed to Rocha, S. P..

3 recordsLinked to original sources

bioRxiv2024

Role of the NOS-cGMP pathways in time-dependent sensitization of behavioral responses in zebrafish

Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in time-dependent sensitization, a behavioral model of translational relevance to trauma and stress-related disorders, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents TDS; blocking NOS-2 90 min after stress also prevents TDS, as does blocking calcium-activated potassium channels in this latter time window. TDS is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce TDS.

neuroscience↗

bioRxiv2019

Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish

Current theories on the role of serotonin (5-HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. This paradoxical, dual role of 5-HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5-HT would produce anxiety-like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5-HT levels in fear-like behavior, as well as in behavior after stimulation. Conspecific alarm substance (CAS) increased bottom-dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post-exposure behavior) showed increased bottom-dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose-dependently decreased fear-like behavior, but increased post-exposure freezing. Metergoline had no effect on fear-like behavior, but blocked the effects of CAS on post-exposure behavior; similar effects were observed with pCPA. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure. These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior towards cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present.

neuroscience↗

bioRxiv2018

Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

Panic disorder (PD) is characterized by abrupt surges of intense fear and distress. There is evidence for a genetic component in this disorder. We ran a meta-analysis of genome-wide association studies of patients with PD, and found 25 single-nucleotide polymorphisms that were associated with the disorder. Causal gene prediction based on these polymorphisms uncovered 20 hits. Exploratory analyses suggested that these genes formed interactor networks, which was enriched in signaling pathways associated with immune and inflammatory responses, as well as growth factors and other developmental mediators. A subset of genes is enriched in limbic regions of the human brain and in microglia and myelinating oligodendrocytes of mice. While these genes were not associated with relevant neurobehavioral phenotypes in mutant mice, expression levels of several causal genes in the amygdala, prefrontal cortex, hippocampus, hypothalamus, and adrenal gland of recombinant mouse strains was associated with endophenotypes of fear conditioning. Drug repositioning prediction was unsuccessful, but this does not discard these genes and pathways as targets for investigational drugs. In general, ASB3, EIF2S2, RASGRF2, and TRMT2B (and its coded proteins) emerged as interesting targets for mechanistic research on PD. These exploratory findings point towards hypotheses of pathogenesis and neuropharmacology that need to be further investigated.

neuroscience↗