Long-term behavioral and NMDA receptor effects of young-adult corticosterone treatment in BDNF heterozygous mice
AuthorKlug, M; Hill, RA; Choy, KHC; Kyrios, M; Hannan, AJ; van den Buuse, M
Source TitleNeurobiology of Disease
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
University of Melbourne Author/sHill, Rachel; van den Buuse, Maarten; Hannan, Anthony; Klug, Maren; Choy, Kwok Ho
AffiliationCentre For Neuroscience Research
Document TypeJournal Article
CitationsKlug, M., Hill, R. A., Choy, K. H. C., Kyrios, M., Hannan, A. J. & van den Buuse, M. (2012). Long-term behavioral and NMDA receptor effects of young-adult corticosterone treatment in BDNF heterozygous mice. NEUROBIOLOGY OF DISEASE, 46 (3), pp.722-731. https://doi.org/10.1016/j.nbd.2012.03.015.
Access StatusThis item is currently not available from this repository
NHMRC Grant codeNHMRC/566879
C1 - Journal Articles Refereed
Psychiatric illnesses, such as schizophrenia, are most likely caused by an interaction between genetic predisposition and environmental factors, including stress during development. The neurotrophin, brain-derived neurotrophic factor (BDNF) has been implicated in this illness as BDNF levels are decreased in the brain of patients with schizophrenia. The aim of the present study was to assess the combined effect of reduced BDNF levels and postnatal stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone. From 6 weeks of age, female and male BDNF heterozygous mice and their wild-type controls were chronically treated with corticosterone in their drinking water for 3 weeks. At 11 weeks of age, male, but not female BDNF heterozygous mice treated with corticosterone exhibited a profound memory deficit in the Y-maze. There were no differences between the groups in baseline prepulse inhibition (PPI), a measure of sensorimotor gating, or its disruption by treatment with MK-801. However, an increase in startle caused by MK-801 treatment was absent in male, but not female BDNF heterozygous mice, irrespective of corticosterone treatment. Analysis of protein levels of the NMDA receptor subunits NR1, NR2A, NR2B and NR2C, showed a marked increase of NR2B levels in the dorsal hippocampus of male BDNF heterozygous mice treated with corticosterone. In the ventral hippocampus, significantly reduced levels of NR2A, NR2B and NR2C were observed in male BDNF heterozygous mice. The NMDA receptor effects in hippocampal sub-regions could be related to the spatial memory deficits and the loss of the effect of MK-801 on startle in these mice, respectively. No significant changes in NMDA receptor subunit levels were observed in any of the female groups. Similarly, no significant changes in levels of BDNF or its receptor, TrkB, were found other than the expected reduced levels of BDNF in heterozygous mice. In conclusion, the data show differential interactive effects of reduced levels of BDNF expression and corticosterone treatment on spatial memory and startle in male and female mice, accompanied by significant, but region-specific changes in NMDA receptor subunit levels in the dorsal and ventral hippocampus. These results could be important for our understanding of the interaction of neurodevelopmental stress and BDNF deficiency in cognitive and anxiety-related symptoms of psychiatric illnesses, such as schizophrenia.
KeywordsCellular Nervous System; Central Nervous System; Nervous System and Disorders
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