Transtorno do estresse pós traumático: uma abordagem experimental
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Data
2008
Autores
Barbosa Neto, Jair Borges [UNIFESP]
Orientadores
Mello, Marcelo Feijó de [UNIFESP]
Tipo
Dissertação de mestrado
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Objetivo: Desenvolver um modelo animal para endofenótipos específicos relacionados aos transtornos de estresse póstraumático (TEPT) e transtorno depressivo maior (TDM) relacionados ao estresse precoce e alterações do eixo HHA. Métodos: Ratos Wistar de ambos os gêneros foram privados de suas mães durante 24 horas no 3° ou 11° dia de vida (PM3 e PM11) e submetidos a choque inescapável quando adolescentes. Ao atingirem a idade adulta realizouse o teste do labirinto em cruz elevado. Foram coletadas amostras de sangue para a medida de corticosterona plasmática em uma condição basal e 15, 30 e 60 minutos após o teste. Os hipocampos destes animais foram isolados e foram quantificadas as monoaminas e os aminoácidos neurotransmissores por HPLC. Resultados: Para as concentrações de corticosterona encontramos um aumento mais robusto nos machos PM11. Os machos do grupo PM3 e as fêmeas do grupo PM11 entraram mais no braço fechado, os machos do grupo PM11 ambularam menos no braço fechado, já as fêmeas PM11 ambularam mais no braço fechado. Os machos PM11NCH apresentaram maiores concentrações de noradrenalina no hipocampo, enquanto que as concentrações de VMA e o “turnover” de NA foram menores nos machos PM3 e PM11 em comparação com os respectivos controles. As fêmeas PM3 e PM11 apresentaram concentrações de NA menores do que o grupo controle. Os machos CH tinham menores concentrações hipocampais de GLU. Os machos PM3 apresentaram concentrações de GABA maiores do que os grupos CTL e PM11 e este último grupo apresentou concentrações menores do que o CTL; os machos CH apresentaram menores concentrações de GABA. As fêmeas PM11 possuíam concentrações menores de GABA do que as fêmeas dos grupos CTL e PM#, que não foram diferentes entre si. Conclusões: O impacto do estressor difere dependendo da maturidade do organismo. Aparentemente os machos privados no 3º dia e as fêmeas no 11o dia são mais ansiosos. A privação materna provocou alterações dos sistemas de transmissão noradrenérgica e serotoninérgica, sendo que machos privados no 11º dia têm uma maior concentração de NA hipocampal, sendo esta diferença marcada entre os que foram estressados com o choque, sugerindo uma semelhança com a clínica dos pacientes com TEPT. Notamos uma alteração paradoxal das concentrações de GABA e GLU entre os machos submetidos ao choque, sugerindo uma alteração da transmissão dos interneurônios gabaérgicos. Os resultados reforçam que devemos nos aprofundar no estudo de endofenótipos específicos, que possam ser mais próximos de nossa realidade clínica.
Objective: to develop an animal model for specific endophenotypes for posttraumatic stress disorder and major depressive disorder related to early life trauma and specific HPA axis dysfunction. Methods: Wistar rats of both genders were separated from their mothers for 24 hours 3 or 11 days after their birth (MD3 or MD11). When they were young adults were submitted to one inescapable shock. At adulthood anxious behavior were accessed using the elevated plus maze test. Basal levels of corticosterone and 15, 30, and 60 minutes after the plus maze test were measured. Hippocampus formation was isolated and HPLC was performed to quantify monoamines and amino acids. Results: a robust elevation of corticosterone levels on males MD11 was found. Male MD3 group and female MD11 group entered more times inside the closed arm; male MD11 group walked less than other groups along the closed arm. Female MD11 group walked more than other groups along closed arm. MD11 males which received shock had higher levels noradrenaline, MD3 and M11 groups had lower VMA levels and NA turnover than controls at hippocampal formation. Females from MD3 and M11 had lower NA levels at hippocampal formation. Males which received shocks had lower glutamate levels at hipocampal formation. Males from MD3 group had lower GABA levels than control and those males from MD11 group and the latest had lower GABA levels than controls. Males which received shocks had lower GABA levels and Females from MD11 group had lower GABA levels at hipocampal formation. Conclusions: The stressors impact will be distinct depending on the organism maturity. It seems that males from MD3 group and females from MD11 group were more anxious. Those early deprived from their mothers showed dysfunctional noradrenergic and serotoninergic systems; males from MD11 group have higher hipocampal NA concentrations, which is even higher for those which received electrical shocks, reinforcing the endophenotype vulnerability model for PTSD related early life stress, but later in childhood, in opposite MDD model related to earlier life stress. A paradoxically GABA and GLU levels alterations among males submitted to shock were observed, suggesting gabaergic interneuron transmission alteration. These results reinforce that we shall study deeper specific endophenotypes, which could be closer to our clinic routine.
Objective: to develop an animal model for specific endophenotypes for posttraumatic stress disorder and major depressive disorder related to early life trauma and specific HPA axis dysfunction. Methods: Wistar rats of both genders were separated from their mothers for 24 hours 3 or 11 days after their birth (MD3 or MD11). When they were young adults were submitted to one inescapable shock. At adulthood anxious behavior were accessed using the elevated plus maze test. Basal levels of corticosterone and 15, 30, and 60 minutes after the plus maze test were measured. Hippocampus formation was isolated and HPLC was performed to quantify monoamines and amino acids. Results: a robust elevation of corticosterone levels on males MD11 was found. Male MD3 group and female MD11 group entered more times inside the closed arm; male MD11 group walked less than other groups along the closed arm. Female MD11 group walked more than other groups along closed arm. MD11 males which received shock had higher levels noradrenaline, MD3 and M11 groups had lower VMA levels and NA turnover than controls at hippocampal formation. Females from MD3 and M11 had lower NA levels at hippocampal formation. Males which received shocks had lower glutamate levels at hipocampal formation. Males from MD3 group had lower GABA levels than control and those males from MD11 group and the latest had lower GABA levels than controls. Males which received shocks had lower GABA levels and Females from MD11 group had lower GABA levels at hipocampal formation. Conclusions: The stressors impact will be distinct depending on the organism maturity. It seems that males from MD3 group and females from MD11 group were more anxious. Those early deprived from their mothers showed dysfunctional noradrenergic and serotoninergic systems; males from MD11 group have higher hipocampal NA concentrations, which is even higher for those which received electrical shocks, reinforcing the endophenotype vulnerability model for PTSD related early life stress, but later in childhood, in opposite MDD model related to earlier life stress. A paradoxically GABA and GLU levels alterations among males submitted to shock were observed, suggesting gabaergic interneuron transmission alteration. These results reinforce that we shall study deeper specific endophenotypes, which could be closer to our clinic routine.
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Citação
BARBOSA NETO, Jair Borges. Transtorno do estresse pós traumático: uma abordagem experimental. Dissertação (Mestrado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2008.