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[Abstract Title]. - Society for Neuroscience

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229. Neuronal and Glial Proliferation III<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm<br />

Program#/Poster#: 229.2/A2<br />

Topic: A.02.a. Proliferation<br />

Support: NIH Grant R15-NS054761<br />

<strong>Title</strong>: Acute chemotherapy treatment yields long-lasting effects on cytogenesis in the mouse<br />

dentate gyrus<br />

Authors: *E. T. WEBER, K. A. VANDERGRIFT, C. M. MONDIE;<br />

Dept Biol, Rider Univ., Lawrenceville, NJ<br />

<strong>Abstract</strong>: The dentate gyrus of mammalian hippocampus is one of the few sites that produce<br />

neuronal progenitor cells in the adult brain. Proliferation in the dentate gyrus is acutely and dosedependently<br />

inhibited 50-75% by the antimitotic chemotherapy agent, thioTEPA, in young adult<br />

(8 weeks old) C57BL/6J mice, as assessed by BrdU immunohistochemistry. In this study, longterm<br />

effects of acute thioTEPA treatment on proliferative capacity in the dentate gyrus and<br />

subsequent per<strong>for</strong>mance in depression-related behavioral tests were examined. Of the BrdUlabeled<br />

cells that survive acute chemotherapy, none appear to persist <strong>for</strong> more than 3 weeks.<br />

Measurements per<strong>for</strong>med at intervals following chemotherapy treatment show an approximate<br />

50% reduction in proliferative capacity in the dentate gyrus that persists <strong>for</strong> at least 12 weeks<br />

after thioTEPA treatment. Assessment of depression-related behavior by tail suspension test<br />

revealed no differences in per<strong>for</strong>mance between mice treated with thioTEPA or with vehicle<br />

when tested up to 12 weeks following treatment, though recent preliminary data suggests a<br />

significant increase when tested 30 weeks following chemotherapy treatment. No significant<br />

differences in per<strong>for</strong>mance in the Porsolt <strong>for</strong>ced swim test were measured up to and including 30<br />

weeks post-treatment.<br />

These results suggest that acute treatment with thioTEPA yields an immediate and long-lasting<br />

effect on the capacity of the pool of progenitor cells in the dentate gyrus to proliferate.<br />

Furthermore, this may yield behavioral effects that are not evident <strong>for</strong> many months beyond<br />

treatment, suggesting a cumulative neurological deficit.<br />

Disclosures: E.T. Weber , None; K.A. Vandergrift, None; C.M. Mondie, None.<br />

Poster<br />

229. Neuronal and Glial Proliferation III<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm

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