Mestrado em Bioquímica

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http://repositorio.ufes.br/handle/10/17562

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Agora exibindo 1 - 6 de 6

Avaliação dos efeitos neuroquímicos e comportamentais do enriquecimento ambiental em animais submetidos a privação maternal
(Universidade Federal do Espírito Santo, 2017-07-14) Lima, Randriely Merscher Sobreira de; Bittencourt, Athelson Stefanon; Bittencourt, Ana Paula Santana de Vasconcellos; Santos, Jeyce Willig Quintino dos; Harres, Vanessa Beijamini; Bortoli, Valquíria Camin de
The relationship between mother and its pups is extremely important for mammals, given the importance of maternal care and attachment in the first days of life. Traumatic events during this period may impair physiological and psychological development, potentially causing short- and long-term changes. Maternal deprivation (MD) is a well-established protocol used to investigate both neurobiological and behavioral changes such as anxiety disorders. It has been demonstrated that environmental enrichment (EE) protocols promote numerous sensory, motor, and cognitive benefits in laboratory animals, and may be used to intervene in changes caused by postnatal adverse events and to prevent the occurrence of psychiatric disorders in adulthood. In this context, we evaluated the implications of EE as a strategy to prevent the maternal deprivation effects on anxiety behaviors and gene expression of the serotonergic system components.
Efeito da separação maternal sobre a impulsividade, consumo voluntário de etanol e expressão de componentes do sistema endocanabinóide e dopaminérgico em córtex pré-frontal e hipocampo : influência do consumo de etanol em binge na adolescência
(Universidade Federal do Espírito Santo, 2016-09-16) Mata, Martielo Januário da; Bittencourt, Ana Paula Santana de Vasconcellos; Dalmaz, Carla; Pires, Rita Gomes Wanderley
Maternal separation is an animal model used to mimic stressful events in the neonatal period, which may lead to the development of cognitive impairments and substances abuse, such as ethanol. This substance is a potential risk to health due to its high consumption by young people, and its consumption alters behavior and neurotransmitter systems function, such as dopaminergic and endocannabinoid systems. In this study, we evaluate the influence of ethanol binge drinking in adolescent rats subjected to maternal separation on learning, impulsivity and voluntary ethanol consumption in adulthood, as well as (the effects of these treatments) on the endocannabinoid and dopaminergic systems. For this, male Wistar rats were separated from their mothers or not (control group) during the postnatal days (DPN) 2-15, for 3 hours daily. Animals not separated were kept on animal facility reared conditions. At DPN 35, the animals were divided in acute or chronic treatment. Both groups were again divided into 3 subgroups, which receive vehicle (saline) or ethanol in doses of 3.0 or 6.0 g/kg by intragastric administration. Ethanol was administered during three consecutive days (acute treatment) or once a day, two consecutive days, interspersed by two days without ethanol, totalizing 10 doses (chronic treatment). At the end of this procedure, the animals were subjected to behavioral tests (learning and impulsivity tests), both using a T-maze, and to the voluntary ethanol consumption test, or euthanized for prefrontal cortex and hippocampus removal. The mRNA expression of the components of the endocannabinoid system: CB1, monoacylglycerol lipase, fatty acid amide hydrolase, N-acylphosphatidylethanolamine phospholipase D and diacylglycerol lipase were evaluated in both structures, and the dopaminergic receptors D1, D2 and tyrosine hydroxylase enzyme were evaluated only in the prefrontal cortex. We observed that maternal separation increased impulsivity behavior and voluntary consumption of ethanol, and ethanol in adolescence impaired short-term memory and appears to reverse other behavioral changes due to maternal separation. In the prefrontal cortex, maternal separation and ethanol altered dopaminergic system with reduction of D1 mRNA expression and increased tyrosine hydroxylase, and appears to increase the enzymes for endocannabinoid synthesis, N-acyl-phosphatidylethanolamine phospholipase D e diacylglycerol 17 lipase. In the hippocampus, the group submitted to both treatments presented a reduction of CB1 mRNA expression and the enzyme N-acylphosphatidylethanolamine phospholipase D, and an increased expression of diacylglycerol lipase. In conclusion, maternal separation and ethanol were able to cause behavioral changes and modifications in endocannabinoid and dopaminergic systems, and maternal separation modifies ethanol effects response.
Efeito de diferentes agonistas de receptores galaninérgicos no núcleo dorsal da rafe de ratos expostos a modelos animais de ansiedade e pânico
(Universidade Federal do Espírito Santo, 2015-02-26) Morais, Juliana da Silva; Harres, Vanessa Beijamini; Bittencourt, Athelson Stefanon; Andreatini, Roberto
Galanin (GAL) is a peptide present in the CNS of various mammals, including human being. Three different receptors have been cloned for the GAL, GALR1 and GALR3, inhibitory, and GALR2, excitatory. The distribution of GAL in structures involved in the control of emotions, and behavior studies suggest that GAL may be involved in the neurobiology of anxiety. The effect seems to depend on both the GAL administration site as involved receptor subtype. The dorsal raphe nucleus (DRN) is distinguished by the presence of serotonergic neurons, important to mediate the antidepressant effect of several drugs. About 40% of the neurons of the DRN co-expressing serotonin and GAL. The activation of GALR1 in this structure decreases the firing rate of serotonergic neurons in the DRN. Previous results from our laboratory showed anxiolytic effect of GAL intra-DRN in rats exposed to the elevated T maze (ETM), but no effect on the escape, related to panic. One of the limitations of this model is that the escape (latency to leave the open arm) usually occurs within a few seconds, so that detect panicogenic effect (low latency escape) can be difficult. Thus, one aim of this study was to investigate the effect of intra-DRN rat GAL in another experimental model of panic, electrical stimulation of the dorsal periaqueductal gray matter (DPAG), more sensitive to detect panicogenic effect. Furthermore, given the existence of different subtypes of galaninergic receptors (GALR1 and GALR2) in the DRN with opposite transduction mechanisms, inhibitory and excitatory, respectively, it is possible that activation of GALR1 receptors is responsible for mediating the anxiolytic/panicogenic effect while activation of GALR2 receptors induces anxiogenic/panicolytic effect. Accordingly, we tested this hypothesis using a selective agonist for GALR1 (M617) and a selective agonist for GALR2 (AR-M1896) in the DRN in rats exposed to ETM. The administration of M617 1.0 and 3.0 nmol in the DRN facilitated inhibitory avoidance, suggesting an anxiogenic-like effect., while administration of AR-M1896 3,0nmoles in the DRN impaired the inhibitory avoidance, suggesting an anxiolytic-like effect, both without changing locomotor activity of animals tested in the open field. Also there was no effect of these drugs on the ETM escape behavior. Later, the pre-treatment with WAY100635 was tested in order to verify that administration of a 5-HT1A antagonist would be able to block the effects seen with GALR2 agonist in animals exposed to ETM. The anxiolytic effect of AR-M1896 was attenuated by the prior administration of WAY100635 at a dose of 0,18nmol. Therefore these results suggest a relationship between the observed effect with the AR-M1896, the release of 5-HT and activation of 5-HT1A receptors. And finally, the GAL 0,3nmol intra-DRN increased significantly the jumpping and trotting thresholds of animals submitted to electrical stimulation of the DPAG, suggesting a panicolytic effect. Together, the results show that the GAL in the DRN participates in the mediation of behavioral responses related to anxiety and, less clearly, to Panic Disorder. The results also shows that effect of GAL on anxiety depends galaninergic subtype receptor activated.
Efeitos do isolamento social neonatal, da fluoxetina e do lactato de sódio sobre o pânico experimental induzido por cianeto de potássio ou estimulação da matéria cinzenta periaquedutal em ratos
(Universidade Federal do Espírito Santo, 2015-08-31) Moraes, Erich Antonio; Schenberg, Luiz Carlos; Harres, Vanessa Beijamini; Sampaio, Karla Nivea
Panic attacks (PAs) can be precipitated either by the inhalation of 5% carbon dioxide (CO2) or by the infusion of 0.5 mol/L sodium lactate (LAC) in predisposed patients, but not in healthy subjects or patients with other psychiatric disorders. These and other observations suggested that PAs are "suffocation false alarms". The panic disorder is likewise characterized by the high comorbidity with childhood separation anxiety (CSA). Consequently, the CSA has been considered both as a predisposing factor of panic and as an important factor of the resistance to panicolitics. Preclinical studies of our laboratory showed, on the other hand, that panicolitics attenuate experimental panic attacks to both the electrical stimulation of the dorsal periaqueductal gray matter (DPAG) and the intravenous injection of potassium cyanide (KCN) in doses and regimenssimilar to those used in the clinics. These studies also showed that neonatal social isolation, a model of CSA, supress the panicolitic effect of fluoxetine (FLX, 1-2 mg.kg-1.dia-1, 21 days) on panic-like responses to electrical stimulation of DPAG. Therefore, the present study evaluated the effects of a higher dose of FLX (Experiment-1) as well as of the infusion of LAC (Experiment-2) on PAs to electrical stimulations of DPAG or to intravenous injections of KCN, respectively, in rats subjected to social isolation as neonates. In Experiment-1, adult male Wistar rats subjected either to 3-h daily neonatal social isolation (NSI) or brief-handling fictive social isolation (FSI) throughout the lactation period, were implanted with electrodes into the DPAG and treated with saline (0.9%, SAL) or fluoxetine (4 mg.kg-1.dia-1, FLX4) over 21 days. Although the panic thresholds remained virtually unchanged in SAL-treated FSI rats, they were progressively increased in SAL-treated NSI rats. Moreover, FLX4-treated rats showed higher thresholds that those treated with SAL. However, comparison to baseline thresholds showed that FLX4 had differential effects on FSI and NSI groups, increasing or reducing thresholds, respectively. Although there were no significant differences between ISF and FSI at the end of the treatment with FLX4, the threshold percent changes relative to baseline suggest that FLX4 had effects even facilitatory on panic responses. The resistance of neonatally-isolated rats to FLX4 extended previous studies with smaller doses of FLX. In turn, the results of Experiment-2 showed that intravenous infusion of a clinically effective concentration of LAC (0.5 mol/L) does not have any effect on the escape responses to KCN in rats either virgin or submitted to the FSI or NSI. Although the latter results suggest that panics to both KCN (experimental) and LAC (clinical) are mediated by different systems, conclusions require further experiments with higher concentrations of LAC.
O papel da galalina na modulação da ansiedade experimental mediada pela matéria cinzenta periaquetutal dorsal (MCPD) de ratos
(Universidade Federal do Espírito Santo, 2014-07-18) Soares, Flávia Roberta Chaves; Harres, Vanessa Beijamini; Bortoli, Valquíria Carmin; Aguiar, Daniele Cristina de
Galanin (GAL) is a 29 amino acids peptide that is present in the CNS of many mammals, including human being. The distribution of GAL and its receptors in emotions control structures involved suggests a possible modulatory role of this neuropeptide on anxiety. The dorsal periaqueductal gray (DPAG) is considered a key structure for behavioral and autonomic expression of defensive behavior. However, the role of GAL in this region has not been studied. The DPAG receives galaninergic projections from other structures, but does not synthesize the peptide on their cell bodies. GAL's actions are mediated by 3 metabotropic receptors, GALR1 and GALR3, which increase K+ efflux, and GALR2, which increases Ca2+ intracellular concentration. Using in situ hybridization technique was described the presence of GALR1 and GalR2 receptors in rat DPAG neurons, but there is GALR1 in greater density. The aim of this study was to investigate the involvement of GAL on the modulation of experimental anxiety by DPAG in rats. Therefore, Wistar rats with a unilateral cannula aimed at the DPAG (AP-lambda: 0 mm; L: 2.0 mm; e P: 4.0 mm, 15o), where the drugs were administered, received the following drugs: GAL (0.1; 0.3; 1.0 e 3.0 nmol/ 0.2μL), M617 – selective agonist GALR1 (0.3; 1.0 e 3.0 nmol/ 0.2μL) e AR-M1896 – selective agonist GALR2 (0.3; 1.0 e 3.0 nmol/ 0.2μL). After 5-7 days of recovery, each animal received an injection of drug and tests were carried-out in the plus-maze, elevated T-maze (ETM) or Vogel Test 20 min later. Each experiment was conducted with separated groups of animals (n=5-12). Tests performed at plus-maze after injection of GAL or selective agonists M617 and AR-M1896 into-DPAG did not change percentage of entries and percentage of time spent in the open arms. The analysis showed that treatment with GAL (3 nmol) significantly impaired Avoidance 2 in the ETM, without change Escape behavior. Acute treatment with GAL did not change locomotion in the Open Field. Finally, GAL (1.0 e 3.0 nmol) did not show difference in the number of punished licks at Conflict Vogel Test in comparison with control group. Thus, the anxiolytic effect of GAL in the DPAG seems to depend on the experimental model of anxiety employee and anxiety level generated by them. Key-words: Galanin. DPAG. Anxiety. T-maze.
Papel da neurotransmissão noradrenérgica da substância cinzenta periaquedutal dorsal na modulação de comportamentos defensivos relacionados aos transtornos de ansiedade generalizada e de pânico
(Universidade Federal do Espírito Santo, 2016-07-19) Carvalho, Johnathan Junior Vaz; Bortoli, Valquíria Camin de; Bittencourt, Ana Paula Santana de Vasconcellos; Aguiar, Daniele Cristina de
The dorsal periaqueductal gray matter (DPAG) is a midbrain structure involved in the mediation of defensive behaviors associated with generalized anxiety disorder (GAD) and panic disorder (PD). There is evidence indicating the involvement of noradrenergic neurotransmission DPAG in the modulation of anxiety, however, there is no evidence for their involvement in panic attacks. In this sense, the objective of this study was to investigate the involvement of noradrenergic neurotransmission DPAG in mediating defensive behaviors related to GAD and PD in the elevated Tmaze (ETM), an animal model that combines the inhibitory avoidance response to GAD and the escape response to PD. For this, Wistar rats were given intra-DPAG administration of noradrenaline (10, 30 or 60 nmol / 0,1μL) or saline and tested in ETM. In addition, we investigated the effect of pre-treatment with intra-DPAG nonselective antagonists of alpha and beta-adrenergic receptors, phentolamine and propranolol, respectively, in effect noradrenaline injection in the same structure. Our results show that intra-DPAG administration of noradrenaline at the highest dose impaired the acquisition of inhibitory avoidance, suggesting an anxiolytic-like effect, but no effect on the escape response in ETM.

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