ORCID Profile
0000-0002-6558-4639
Current Organisation
Universidade Federal de Minas Gerais Faculdade de Medicina
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Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.NEUROSCIENCE.2005.12.023
Abstract: GABA is an important inhibitory transmitter in the CNS. In the enteric nervous system, however, both excitatory and inhibitory actions have been reported. Here, we investigated the effects of GABA on the intracellular Ca2+ concentration of guinea-pig myenteric neurons (at 35 degrees C) using Fura-2-AM. Neurons were identified by 75 mM K+ depolarization (5 s), which evoked a transient intracellular Ca2+ concentration increase. GABA (10 s) induced a dose dependent (5 nM-1 microM) transient intracellular Ca2+ concentration rise in the majority of neurons (500 nM GABA: 251+/-17 nM, n=232/289). Interestingly, the response to 5 microM GABA (n=18) lasted several minutes and did not fully recover. GABA response litudes were significantly (P<0.001) reduced by GABAA and GABAB receptor antagonists (10 microM) bicuculline and phaclofen. The GABAA agonist isoguvacine (10 microM) and GABAB agonist baclofen (10 microM) induced similar responses as 50 nM GABA, while the GABAC agonist cis-4-aminocrotonic acid (CACA) (10 microM) only elicited small responses in a minority of neurons. Removal of extracellular Ca2+ abolished all responses while depletion of intracellular Ca2+ stores by thapsigargin (5 microM) did not alter the responses to 500 nM GABA (n=13), but reduction of Ca2+ influx through voltage-dependent Ca2+ channels did. The nicotinic antagonist hexamethonium (100 microM) also reduced GABA responses by almost 70% suggesting that GABA stimulates cholinergic pathways, while the purinergic receptor blocker pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) and the 5-HT3 receptor blocker ondansetron only had minor effects. GABA elicits transient intracellular Ca2+ concentration responses in the majority of myenteric neurons through activation of GABAA and GABAB receptors and much of the response can be attributed to facilitation of ACh release. Thus GABA may act mainly as a modulator that sets the state of excitability of the enteric nerve network. A concentration of 5 microM GABA, although frequently used in pharmacological experiments, seems to cause a detrimental response reminiscent of the neurotoxic effects glutamate has in the CNS.
Publisher: EDITORA SCIENTIFIC
Date: 03-2010
Publisher: Cold Spring Harbor Laboratory
Date: 17-04-2020
DOI: 10.1101/2020.04.13.20063404
Abstract: Major depressive disorder (MDD) is a debilitating illness characterized by the persistence of negative thoughts and emotions. Although antidepressant medications are effective, less than half of patients achieve complete remission despite multiple treatment trials. Repetitive transcranial magnetic stimulation (rTMS) has proven effective in the treatment of depression, especially for patients resistant to antidepressant medications. Remission rates when using rTMS for treatment-resistant depression (TRD) patients are between 30% and 40%. The responsiveness to pharmacotherapy and rTMS therapy may be influenced by genetic factors. Here we aim to characterize the genetic profile of refractory in iduals with MDD and their rTMS responsiveness. We used an extreme-phenotype design (rTMS responders vs. non-responders) and conducted a genome wide association study on 48 participants and 593,260 SNPs. We identified 53 significant SNP associations. Gene-set enrichment analysis showed that significantly associated genes loaded onto synaptic plasticity regulation pathways. Among the genes found differentially expressed in rTMS responders compared to non-responders were APP, GRID2 and SPPL2A genes. Based on these findings, we suggest that the identified genes may influence of rTMS responsiveness. Furthermore, the rTMS responsiveness may be associated with several pathways and not just to the influence of a single gene. To the best of our knowledge, this is the first report on the genetic profile of rTMS response using a GWAS approach. Nevertheless, further studies are necessary to enlight the molecular mechanism by which these genes affect response to rTMS treatment.
Publisher: EDITORA SCIENTIFIC
Date: 06-2009
DOI: 10.1590/S1516-44462009000200013
Abstract: OBJECTIVE AND METHOD: A large increase in the number of Brazilian studies on psychiatric genetics has been observed in the 1970's since the first publications conducted by a group of researchers in Brazil. Here we reviewed the literature and evaluated the advantages and difficulties of psychiatric genetic studies in the Brazilian population. CONCLUSION: The Brazilian population is one of the most heterogeneous populations in the world, formed mainly by the admixture between European, African and Native American populations. Although the admixture process is not a particularity of the Brazilian population, much of the history and social development in Brazil underlies the ethnic melting pot we observe nowadays. Such ethnical heterogeneity of the Brazilian population obviously brings some problems when performing genetic studies. However, the Brazilian population offers a number of particular characteristics that are of major interest when genetic studies are carried out, such as the presence of isolated populations. Thus, differences in the genetic profile and in the exposure to environmental risks may result in different interactions and pathways to psychopathology.
Publisher: FapUNIFESP (SciELO)
Date: 2006
DOI: 10.1590/S0047-20852006000400005
Abstract: OBJETIVO: Nos últimos anos, o papel dos genes dos sistemas serotoninérgicos e dopaminérgicos tem sido sistematicamente investigado em pacientes com transtorno obsessivo-compulsivo (TOC), uma vez que esses neurotransmissores apresentam uma provável implicação na fisiopatologia do TOC. Este artigo objetiva revisar os principais resultados de estudos de associação entre genes candidatos e TOC. MÉTODOS: Revisão da literatura na base de dados Medline até agosto de 2006, utilizando as palavras-chave obsessive-compulsive disorder (OCD) e/ou gene(s), polymorphism(s), genetics. RESULTADOS: Inúmeros estudos têm apresentado resultados negativos ao compararem pacientes com TOC e controles, entretanto resultados positivos têm sido observados em pacientes com TOC com características clínicas particulares (sexo, idade de início, dimensão ou gravidade dos sintomas obsessivos ou compulsivos e presença de tiques). CONCLUSÃO: Para garantir a continuidade do avanço de estudos genéticos, é necessária a identificação de subgrupos homogêneos de pacientes com TOC. Diante desses grupos, será possível delinear endofenótipos confiáveis que permitam explorar de forma mais específica a contribuição dos diferentes genes na patogênese da doença.
Location: Brazil
Location: Brazil
No related grants have been discovered for Marco Romano-Silva.