Molecular neuroscienceAntidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: Differential regulation of specific exons by antidepressants and corticosterone
Section snippets
Animals
Virus-free Sprague–Dawley male rats initially weighing 220–250 g were used. Rats were housed in groups of three under standard laboratory conditions (temperature 21±1 °C, humidity 55±5%, 12-h light/dark cycle). Animals were provided free access to food. Rats were acclimatized for one week before the start of experiments. Each treatment group contained six rats.
Corticosterone treatment
All the experiments were carried out in accordance with the National Institutes of Health guide for the care and use of laboratory
Serum corticosterone levels
Serum corticosterone levels were measured in sham, corticosterone-treated and corticosterone-treated rats given antidepressants. We also measured serum corticosterone levels in normal and antidepressant-treated rats. The serum corticosterone levels are given in Table 1. As in our earlier studies, we found that corticosterone level was significantly higher in corticosterone pellet-implanted rats (Dwivedi and Pandey 2000, Dwivedi et al 2000), and that desipramine or phenelzine normalized the
Discussion
This comprehensive examination of the effects of corticosterone or antidepressants, and of antidepressant effects of corticosterone on BDNF in rat brain, which showed deceptively simple results of decrease versus increase in total BDNF, revealed complex regulation processes when the effects on individual BDNF exons were examined (Table 2).
Conclusion
In conclusion, our study for the first time reveals the regulation of selective BDNF exons by corticosterone and also suggests that there is a complex interaction between antidepressants and corticosterone in regulating BDNF exons. We observed that the various classes of antidepressants administered chronically to rats increase different exons, which suggests that there is no unified mechanism of regulation of BDNF by antidepressants. In addition, antidepressants also regulate BDNF exons other
Acknowledgments
This work was supported by RO1MH68777 from the National Institute of Mental Health and a Career Development Award (KO1MH 01836) from the National Institute of Mental Health to Dr. Yogesh Dwivedi and by RO1MH56528 from the National Institute of Mental Health to Dr. G. N. Pandey. Technical assistance provided by Ms. Miljana Petkovic is acknowledged.
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