Da Silva

GROUP LEADER NAME (as it appears in publications): Rosane Souza da Silva cited as Da Silva RS

AFFILIATION: Pontifícia Universidade Católica do Rio Grande do Sul

TEL:* +55 51 3320 3500 ext. 41458

FAX:* +55 51 3320 3545

EMAIL:* rosane.silva@pucrs.br

WEB: www.pucrs.br/uni/poa/fabio/neuropsicofarmaco.html

GROUP NAME / RESEARCH INTEREST IN FEW WORDS:

Purinergic system during brain development

Study of the modulatory role of adenosine and adenosine receptors in brain development.

SHORT SUMMARY OF RESEARCH INTEREST (MAX. 200 WORDS):

Note: please attach at the end of the form a longer description, with a maximum of 2000 words.

A variety of intra and extracellular modulators are mandatory to the correct development of Central Nervous system. Adenosine appears as a potent modulator of brain development. Adenosine plays its actions through specific receptors named P1 (A1, A2A, A2B and A3). The activation of P1 receptors subtypes and consequently the biochemical cascade triggered depends on the extracellular concentration of adenosine. This is a consequence of the opposite functions of adenosine receptors. A1 and A3 are inhibitory receptors and A2A and A2B are excitatory ones. The main function of adenosine in CNS is the control of neurotransmitters release and function. Considering the expression of adenosine receptors since early stages of development and the potential of neuromodulation exerted by adenosine the main research interest of our group is (1) to evaluate the effects of adenosine neuromodulation disruption during brain development in biochemical and behavioral parameters; (2) to evaluate the impact of adenosine neuromodulation disruption during brain development to the response to drugs of abuse.

LIST OF UP TO FIVE RELEVANT PUBLICATIONS:

1- Profile of nucleotide catabolism and ectonucleotidase expression from the hippocampi of neonatal rats after caffeine exposure. DA SILVA, R ; Richetti, SK ; TONIAL, E. M. ; BOGO, M. R. ; BONAN, C. D. Neurochemical Research. Accepted in August 3th, 2011.

2- Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets. Rico EP, Rosemberg DB, Seibt KJ, Capiotti KM, Da Silva RS and Bonan CD. Zebrafish Special Issue. Neurotoxicology and Teratology. Accepted in July 22, 2011.

3- Neonatal morphine exposure alters E-NTPDase activity and gene expression pattern in spinal cord and cerebral cortex of rats. Rozisky JR, da Silva RS, Adachi LS, Capiotti KM, Ramos DB, Bogo MR, Bonan CD, Sarkis JJ, Torres IL. Eur J Pharmacol. 2010 Sep 10; 642(1-3):72-6.

4- Effects of arsenic (As) exposure on the antioxidant status of gills of the zebrafish Danio rerio (Cyprinidae). Ventura-Lima J, de Castro MR, Acosta D, Fattorini D, Regoli F, de Carvalho LM, Bohrer D, Geracitano LA, Barros DM, Marins LF, da Silva RS, Bonan CD, Bogo MR, Monserrat JM. Comp Biochem Physiol C Toxicol Pharmacol. 2009 May;149(4):538-43.

5- Maternal caffeine intake affects acetylcholinesterase in hippocampus of neonate rats. Da Silva RS, Richetti SK, da Silveira VG, Battastini AM, Bogo MR, Lara DR, Bonan CD. Int J Dev Neurosci. 2008 May-Jun;26(3-4):339-43.

6- Maternal caffeine intake impairs MK-801-induced hyperlocomotion in young rats. Da Silva RS, Hoffman A, de Souza DO, Lara DR, Bonan CD. Eur J Pharmacol. 2005 Feb 21;509(2-3):155-9.

GROUP MEMBERS (NAME, POSITION, EMAIL):*

1- Rosane Souza da Silva – Researcher

2- Luiza Reali Nazario – Undergraduate student

3- Rachel Lima de Jesus - Undergraduated student

4 – Lidiane Fazenda – Undergraduated Student

5 - Milene Dornelles Luzardo - Undergraduated Student

6- Luana Couto - Undergraduated Student

FISH FACILITIES (TYPE OF FISH SYSTEM/TANKS, CAPACITY, ETC.)*

01 Shelf Stand-alone System from Tecniplast

01 Shelf Stand-alone System from Aquatic Habitats

01 MEEPS tank System from Aquatic Habitats

50 Glass tanks (approximately)

FISH LINES KEPT IN STOCK:*

Wild type

OTHER EQUIPMENT RELATED TO ZEBRAFISH RESEARCH*

01 Microinjector system

LAB EXPERTISE AND TECHNICAL CAPABILITIES (RELATED TO ZEBRAFISH RESEARCH)*

Fish maintenance and reproduction protocols.

Microinjection in zebrafish embryos.

Western Blot using zebrafish tissues samples.

Pharmacological and toxicological exposure protocols: Psychoactive drugs and metals

Behavioral tasks

Evaluation of Enzymatic activities: Acetylcholinesterase; Ectonucleotidases, Adenosine deaminase

Evaluation of mRNA expression by Real-Time: Genes related to purinergic system and its targets.

Temporally knockdown with morpholinos anti-sense

OTHER RELEVANT INFORMATION:*

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Research Interesting

Adenosine, as a natural constituent of intra and extracellular medium, plays multiple effects on a diversity of organs and cells. At intracellular medium, adenosine plays a homeostatic role while at extracellular medium adenosine can acts as a modulator of cell differentiation, proliferation and activity. Extracellular adenosine induces its intracellular effects through activation of P1 receptors subtypes (A1, A2A, A2B, and, A3) which has a different patterns of tissue expression, distinct ligand binding properties and G protein coupling, well described in mammals and in lesser extension in other vertebrates and invertebrates. A1 and A3 adenosine receptors are coupled to inhibitory G proteins whereas A2A and A2B are linked to excitatory ones. The signal pathways triggered by adenosine receptors involve control of phosphatases and kinases activities, ion channels function and gene expression. DARPP-32, a phosphoprotein, is one of the intracellular mechanism of adenosine signaling, which is shared by several drugs, such as caffeine, alcohol and nicotine.

During the complex phase of initial development, adenosine plays differential role from that observed in adults. While its increase during brain ischemia in adult mammals promotes neuroprotection through A1 adenosine receptor, in neonates a lack of its effects was showed. Immature A2A adenosine receptors knockout mice developed increased neurological damage after hypoxic ischemia, suggesting a beneficial role for adenosine during hypoxic ischemia. In opposite way, adult mice receiving A2A adenosine receptor antagonist and adult A2A adenosine receptors knockout mice exhibited adenosine neuroprotective effects. Also, during prenatal life, the adenosinergic system is the dominant humoral regulator of cardiac function, and activation of adenosine A1 receptors may result in cardiac hypoplasia. Adenosine receptors are also related to neurodegenerative diseases as Alzheimer and Parkinson and antagonists of adenosine receptor A2A has been related to promote decrease of neurodegenerative features of these disorders.

As adenosine can play several important roles in neurodevelopment and response to drug our group is interested in (1) to evaluate the effects of adenosine neuromodulation disruption during brain development through biochemical and behavioral parameters assessment; (2) to evaluate the impact of adenosine neuromodulation disruption during brain development to the response to drugs of abuse.

These aims have been reached through (1) exposure of zebrafish embryos to inhibitors of adenosine signaling; (2) evaluation of the enzymatic pathway that controls adenosine production. This pathway is composed by NTPDases, 5’-nucleotidases and ecto-adenosine deaminase; (3) evaluation of gene expression of components of adenosinergic system; and (4) evaluation of tolerance and cross-sensitization between drugs of abuse and adenosine receptors agonists and antagonists.