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Memória do medo condicionado ao contexto : alterações por inibição da síntese proteica ou por bloqueio de receptores de glutamato do tipo NMDA no hipocampo / Retrieval of the aversive memory : impairments by protein synthesis inhibition or blockade of NMDA glutamatergic receptor in the hippocampusSperandeo, Maria Luiza Antunes, 1949- 28 August 2013 (has links)
Orientador: Elenice Aparecida de Moraes Ferrari / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T21:27:10Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013 / Resumo: O estudo do condicionamento clássico aversivo contribuiu para caracterizar as fases da formação da memória (aquisição, consolidação, reconsolidação, persistência e extinção) e os mecanismos de plasticidade neuronal subjacentes. Entre estes, a ativação de receptores glutamatérgicos NMDA, de transcrição gênica e síntese proteica parecem fundamentais. O fator neurotrófico derivado de cérebro (BDNF) e o gene de expressão imediata (IEG) zenk são ativados no hipocampo de mamíferos durante a reconsolidação e a extinção. Este estudo investigou os efeitos da inibição da síntese proteica e do bloqueio dos receptores NMDA no hipocampo de pombos na reconsolidação e extinção da memória de medo contextual. No Experimento 1, pombos foram condicionados, testados ao contexto (reativação), submetidos à infusão intra-hipocampo de salina (SAL-PR), de anisomicina (ANI-PR) ou de MK-801 (MK-PR) após o teste (pós-reativação; PR), e retestados 2 dias depois (Rt 2d). No Experimento 2, três grupos tiveram um segundo reteste, 9 dias após a infusão (Rt 9d), enquanto que outros três grupos não passaram pelo teste (sem reativação- SR). O treino (20 min) teve três pareamentos som-choque. No teste e no Rt 2d houve exposição ao contexto do condicionamento por 5 min e no reteste Rt 9d, por 30 min. Nos dois experimentos, todos os grupos apresentaram alta ocorrência de congelamento (CONG) nas sessões de treino e de teste, mas no Rt 2d os grupos ANI-PR e MK-PR mostraram uma redução significativa de CONG (p < 0,05). Os grupos SR exibiram alta ocorrência de CONG tanto no Rt 2d, quanto no início do Rt 9d (p > 0,05). No Rt 9d o grupo MK-PR não teve recuperação espontânea de CONG, sugerindo prejuízo irreversível provocado pelo MK-801 na memória de medo contextual. Os grupos, SAL-PR, SAL-SR, ANI-PR, ANI-SR e MK-SR mostraram diminuição gradual de CONG durante a sessão de Rt 9d, evidenciando a extinção. Análises com Western blotting após o Rt 9d indicaram que o conteúdo de BDNF-maduro no hipocampo dos pombos SAL-PR foi significativamente maior em comparação aos demais grupos (p < 0,05), mas não foram observadas diferenças entre os grupos para o Zenk (p > 0,05). Isso sugere a participação do BDNF hipocampal na reconsolidação e na extinção da memória de medo contextual em pombos. Assim, a inibição da síntese proteica e o bloqueio dos receptores NMDA no hipocampo de pombos, após o teste ao contexto, prejudicaram a reconsolidação da memória de medo condicionado ao contexto. Além disso, os prejuízos observados foram dependentes da reativação da memória durante o teste / Abstract: The study of classical aversive conditioning has contributed to the characterization of different phases in memory formation (acquisition, consolidation, reconsolidation, extinction and persistence) and the underlying mechanisms of neuronal plasticity. Among these, the activation of NMDA glutamate receptors, gene transcription and protein synthesis are pointed as essentials. The brain-derived neurotrophic factor (BDNF) and immediate expression gene (IEG) zenk are activated in the hippocampus of mammals during reconsolidation and extinction. This study investigated the effects of protein synthesis inhibition and blockade of NMDA receptors in the hippocampus of pigeons on reconsolidation and extinction of contextual fear memory. In Experiment 1, pigeons were conditioned, tested in the context (reactivation), received intra-hippocampus infusion of saline (SAL-PR), anisomycin (ANI-PR) or MK-801 (MK-PR) after the test (post-reactivation, PR), and had a retest two days later (Rt 2d). Experiment 2, had a retest 9 days after intra-hippocampus infusion (Rt 9d) for three PR groups, and other three groups that were not tested 24h after training served as control for reactivation (no reactivation-NR). Three tone-shock pairings were presented during training (20 min). Pigeons were exposed to the context during 5 min in the test and Rt 2d sessions and during 30 min in Rt 9d. In both experiments, the occurrence of freezing (FRZ) was high in training and testing sessions for all the groups, but ANI-PR and MK-PR pigeons showed a significant decrease in FRZ during the Rt 2d (p < 0.05). The NR groups exhibited high occurrence of FRZ both in the Rt 2d and in the beginning of Rt 9d (p > 0.05). MK-PR pigeons had no spontaneous recovery of FRZ, suggesting irreversible impairment caused by MK-801 in contextual fear memory. The groups, SAL-PR, SAL-NR, ANI-PR, ANI-NR and MK-NR showed a gradual decrease in FRZ during the Rt 9d session, evidencing extinction. Western Blotting analysis indicated that the content of mature BDNF in the hippocampus of SAL-PR group after Rt 9d session was higher than that seen for the other groups (p < 0.05), but no between-group differences for Zenk were observed (p > 0.05). This suggests the involvement of hippocampal BDNF in reconsolidation and extinction of contextual fear memory in pigeons. The present data show that inhibition of protein synthesis and blockade of NMDA receptors in the hippocampus of pigeons, after the testing session to context, impaired reconsolidation of contextual fear conditioning memory and affected the process of extinction. Furthermore, the impairments were dependent on the reactivation of fear memory during the test / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular
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N-Methyl-D-Aspartat-Antagonisten induzierten apoptotische Zelluntergänge im Gehirn junger RattenMiksa, Michael 06 April 2004 (has links)
Der wichtigste exzitatorische Neurotransmitter Glutamat spielt eine grosse Rolle in der Gehirnentwicklung, wie neuronale Migration und Synaptogenese. Ob glutamaterge Stimulation für das Überleben entwickelnder Neuronen notwendig ist, war bislang jedoch unbekannt. Um zu untersuchen, ob eine Hemmung von Glutamatrezeptoren im unreifen Gehirn zu Neurodegeneration führt, wurden Ratten im Alter von 1 bis 31 Tagen für 24 Stunden mit dem N-Methyl-D-Aspartat-(NMDA) Glutamatrezeptorantagonisten Dizocilpin (MK801) behandelt. Die Dichte neuronaler Degeneration wurde mikroskopisch in Kupfer-Silber- und TUNEL- gefärbten Hirnschnittpräparaten ermittelt und Unterschiede mittels ANOVA analysiert (Signifikanzniveau p / The predominant excitatory neurotransmitter glutamate plays a major role in certain aspects of neural development. However, whether developing neurons depend on glutamate for survival remains unknown. To investigate if deprivation of glutamate stimulation in the immature mammalian brain causes neuronal cell death (apoptosis), rat pups aged 0 to 30 days were treated for 24 hours with dizocilpine maleate (MK801), an N-methyl-D-aspartate-(NMDA) glutamate receptor antagonist. Density of neural degeneration was evaluated by a stereological dissector method in cupric-silver and TUNEL-stained brain slices. Groups were compared by ANOVA and significance considered at p
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