RESUMO
BACKGROUND: Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). OBJECTIVE: The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. METHODS: Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. RESULTS: Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. CONCLUSIONS: The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT.
Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Memória/fisiologia , Convulsões/fisiopatologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Hormônio Liberador da Corticotropina/metabolismo , Transtorno Depressivo/psicologia , Masculino , Atividade Motora/fisiologia , Distribuição Aleatória , Ratos Endogâmicos WKY , Ratos Wistar , Convulsões/etiologia , Especificidade da Espécie , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Serum brain-derived neurotrophic factor (BDNF) protein has been related to depression and less consistently to its treatments in human studies. However, animal studies have failed to demonstrate a clear link between BDNF protein in serum and brain tissue. METHODS: Serum and brain tissue levels of BDNF protein were measured with ELISA in the Wistar-Kyoto (WKY) and Wistar strains at 1 and 7 days after 5 daily electroconvulsive stimulus sessions or sham treatments. RESULTS: The WKY strain showed lower baseline serum BDNF protein relative to Wistar controls. After 5 electroconvulsive stimuli, BDNF protein density was significantly increased in hippocampus and cortical regions, but not in the cerebellum or in serum. A clear correlation between brain and serum BDNF was not observed in either strain or treatment group. DISCUSSION: Despite lower baseline serum BDNF protein in the WKY strain, a lack of change in serum BDNF after electroconvulsive stimulus and a lack of correlation between brain and serum BDNF protein calls into question the relevance of serum BDNF as a measure of depression and treatment response.
