Corticosterone effects on BDNF expression in the hippocampus. Implications for memory formation.
The adrenal steroid corticosterone has profound effect on the structure and function of the hippocampus. Probably as a result of that, it modulates memory formation. In this review, the question is addressed if the corticosterone effects on memory processes are mediated by alterations in the expression of the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) in the hippocampus. First, studies are described investigating the effect of corticosterone on BDNF expression in the rat hippocampus. It appears that corticosterone suppresses the BDNF expression at the mRNA and protein level in a subfield-specific way. Second, a model for the mechanism of action is proposed. In this model, activated mineralocorticoid and glucocorticoid receptors repress transcriptional activity of the BDNF promoter site-specifically via interaction with other transcription factors. Third, the implications for learning and memory are discussed. Studies show that during water maze training, corticosterone levels rise significantly, but the BDNF expression is not suppressed in any hippocampal subfield. Furthermore, high BDNF expression levels in specific subfields correlate with a good memory performance. Therefore, we suggest that the resistance of the hippocampal BDNF expression to suppression by corticosterone, as seen after water maze training, may contribute to an optimal memory performance.
Leiden/Amsterdam Center for Drug Research, Division of Medical Pharmacology, Sylvius Laboratories, P.O. Box 9503, 2300 RA Leiden, The Netherlands.
M J
MJ
Schaaf
E R
ER
De Kloet
E
E
Vreugdenhil
D000315:Adrenalectomy; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000099052:CRF Receptor, Type 1
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012702:Serotonin Antagonists; D000099052:CRF Receptor, Type 1; D007608:Kainic Acid; D003345:Corticosterone