Reconsolida??o da mem?ria de extin??o : an?lise farmacol?gica, bioqu?mica e molecular

• Main Author: Radiske, Andressa
• Other Authors: Silva Filho, Ir?nio Gomes da
• Format: Others
• Language: Portuguese
• Published: Pontif?cia Universidade Cat?lica do Rio Grande do Sul 2015
• Subjects: MEDICINA; NEUROCI?NCIA; MEM?RIA; HIPOCAMPO; CIENCIAS DA SAUDE::MEDICINA
• Online Access: http://tede2.pucrs.br/tede2/handle/tede/6217

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([e-mail]) on 2015-07-15T15:03:02Z No. of bitstreams: 1 472298 - Texto Completo.pdf: 677948 bytes, checksum: 96bddf252e88732ab099f3a5a6fc7a54 (MD5) === Made available in DSpace on 2015-07-15T15:03:02Z (GMT). No. of bitstreams: 1 472298 - Texto Completo.pdf: 677948 bytes, checksum: 96bddf252e88732ab099f3a5a6fc7a54 (MD5) Previous issue date: 2015-05-08 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES === Background : Therapies based on the impairment of memory reconsolidation or the enhancement of extinction learning offer the possibility of diminishing the impact caused by the persistent recollection of traumatic events. Nonetheless, the possible interaction between reconsolidation and extinction has rarely been considered. Previously, we reported that reactivation induces reconsolidation of fear extinction, but the molecular bases of this process are largely unknown. Brain-derived neurotrophic factor (BDNF) has been repeatedly linked to fear extinction; therefore we analyzed the possible involvement of this neurotrophin in fear extinction memory reconsolidation. Methods : With a step-down inhibitory avoidance-learning task (IA) and selective pharmacological tools, we investigated the effect of gene expression, protein synthesis and BDNF signaling inhibition on the persistent storage of the reactivated fear extinction memory trace in rats. Results : When given in dorsal CA1 immediately after IA extinction reactivation, the protein synthesis inhibitor anisomycin (ANI), the gene expression inhibitor ?- amanitin (AMA), the BDNF maturation blocker PAI-1, and function-blocking anti- BDNF antibody hindered extinction memory persistence. Pro-BDNF and BDNF levels were altered in dorsal CA1 after extinction memory reactivation. Coinfusion of recombinant BDNF reversed the recovery of fear induced by intra-CA1 ANI and AMA. Conclusion : These data suggest that hippocampal BDNF is sufficient to sustain fear extinction memory reconsolidation and indicate that increasing BDNF signaling after extinction memory retrieval impedes the recurrence of fear caused by impairing this process. === Introdu??o : Terapias baseadas no bloqueio da reconsolida??o ou no fortalecimento da extin??o oferecem a possibilidade terap?utica de diminuir o impacto causado pela persist?ncia das lembran?as de eventos traum?ticos. No entanto, a intera??o entre a reconsolida??o e a extin??o tem sido pouco analisada. Previamente, nosso grupo demonstrou que a mem?ria de extin??o do medo pode ser reconsolidada, por?m as bases moleculares que sustentam esse processo ainda s?o desconhecidas. O fator neurotr?fico dependente do c?rebro (BDNF) tem sido frequentemente relacionado com a extin??o do medo; por isso, n?s analisamos o poss?vel envolvimento dessa neurotrofina na reconsolida??o da mem?ria de extin??o do medo. M?todos : Com a tarefa de esquiva inibit?ria como modelo experimental junto com ferramentas farmacol?gicas espec?ficas, n?s investigamos o efeito da express?o g?nica, s?ntese de prote?nas e da inibi??o da sinaliza??o de BDNF sobre a persist?ncia da mem?ria de extin??o ap?s a sua reativa??o em ratos. Resultados : Quando injetado imediatamente ap?s a reativa??o da mem?ria de extin??o, o inibidor de s?ntese proteica anisomicina (ANI), inibidor de express?o g?nica ?-amanitina (AMA), o bloqueador da matura??o de BDNF (PAI-1) e um anticorpo bloqueador da fun??o de BDNF (anti-BDNF), prejudicaram a persist?ncia da mem?ria de extin??o. Os n?veis de pr?-BDNF, BDNF e pTrKB foram alterados na regi?o CA1 do hipocampo dorsal ap?s a reativa??o da mem?ria de extin??o. A Co-infus?o de BDNF recombinante reverteu o reaparecimento do medo induzido pela infus?o de ANI e AMA na regi?o CA1 do hipocampo dorsal. Conclus?o : Esses dados sugerem que o BDNF hipocampal ? suficiente para sustentar a reconsolida??o da mem?ria de extin??o do medo e indicam que o aumento da sua sinaliza??o ap?s a reativa??o da mem?ria de extin??o impede a reincid?ncia do medo causado por inibidores desse processo.