Time-dependent effects of the TrkB agonist, 7,8-dihydroxyflavone, on spatial learning in the rat.
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1
Trinity College Dublin, Department of Physiology, Ireland
Physical exercise is an established stimulus for neurogenesis and synaptogenesis; morphological changes that are reported to underpin certain types of learning and memory. Previous studies in our laboratory1 have shown that one week of exercise enhances hippocampal-dependent learning in the rat, when learning occurs immediately post-exercise. This was associated with increased cell proliferation, the first step in the four-week long process of neurogenesis. This cognitive enhancement was also observed following intracerebroventricular administration of Brain-derived Neurotrophic Factor (BDNF); a neurotrophin which predominantly acts at the TrkB receptor.
7,8-dihydroxyflavone (7,8-DHF) is recognised as a robust TrkB receptor agonist2. In this study, we assess the persistence of the effects of TrkB receptor activation on learning and memory by testing spatial memory both 48hours and 23days following intraperitoneal administration of 7,8-DHF; the latter time point coinciding with the integration of new neurons into the circuitry, as they reach a stage of functional maturity.
Male Han Wistar rats (n=28) were randomly divided into 2 groups; Vehicle (Veh n=14) and 7,8-DHF-treated (n=14) and further subdivided into day 9 or day 30 cognitive testing groups. Each animal received a daily IP injection of either 7,8-DHF (500ul; 5mg/kg in 0.9% NaCl solution) or vehicle solution (0.9% NaCl) for 7 days (days 1-7). Injections of BrdU (500ul; 50mg/kg in 0.9% saline solution); a thymidine analogue that labels the DNA of dividing cells, were also administered daily following 7,8-DHF or vehicle injection. Half of the Veh and 7,8-DHF groups (n=7 per group) were trained in an Object Displacement (OD) Task, a test of spatial learning, on day 8, tested on Day 9 and killed immediately following testing. The other half remained in the home cage, were trained in the task on day 29, tested on day 30 and killed immediately following testing. Brains were hemisected; one hemisphere was processed for analysis of BrdU by immunocytochemistry. Dentate Gyrus, hippocampus, and entorhinal cortex were subdissected free from the other hemisphere, and prepared for Western Blot analysis, ELISA, and PCR.
To date, behavioural analysis shows that the 7,8-DHF group displayed significantly enhanced cognitive function on Day 30 compared to Vehicle controls (p<0.05; 2-way ANOVA), but this enhancement was not observed in 7,8-DHF animals tested on Day 9. The timing of these experiments indicates that the mechanism underlying this cognitive enhancement may involve neurogenesis. Tissue is presently being analysed to test this hypothesis.
Acknowledgements
Funded by TCD Studentship Award, Trinity College Dublin
References
1 É. W. Griffin, R. G. Bechara, A. M. Birch, and Á. M. Kelly, 'Exercise Enhances Hippocampal-Dependent Learning in the Rat: Evidence for a Bdnf-Related Mechanism', Hippocampus, 19 (2009), 973-80.
2 Sung-Wuk Jang, Xia Liu, Manuel Yepes, Kennie R. Shepherd, Gary W. Miller, Yang Liu, W. David Wilson, Ge Xiao, Bruno Blanchi, Yi E. Sun, and Keqiang Ye, 'A Selective Trkb Agonist with Potent Neurotrophic Activities by 7,8-Dihydroxyflavone', Proceedings of the National Academy of Sciences, 107 (2010), 2687-92.
Keywords:
78-DHF,
Spatial learning,
78-dihydroxyflavone,
TrkB agonist,
Memory
Conference:
Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014.
Presentation Type:
Poster Presentation
Topic:
Early Career Neuroscience
Citation:
Hennessy
R,
Prenderville
J,
Kerley
R,
Mota
B and
Kelly
ÁM
(2014). Time-dependent effects of the TrkB agonist, 7,8-dihydroxyflavone, on spatial learning in the rat..
Front. Neurosci.
Conference Abstract:
Neuroscience Ireland Young Neuroscientists Symposium 2014 .
doi: 10.3389/conf.fnins.2014.87.00012
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Received:
10 Sep 2014;
Published Online:
10 Sep 2014.
*
Correspondence:
Ms. Ruth Hennessy, Trinity College Dublin, Department of Physiology, Dublin, Dublin 2, Ireland, hennesr@tcd.ie