This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, G. D. Articles by Ingram, D. K. Search for Related Content PubMed PubMed Citation Articles by Lee, G. D. Articles by Ingram, D. K.

Transient Improvement in Cognitive Function and Synaptic Plasticity in Rats Following Cancer Chemotherapy

Authors' Affiliations: ¹ Laboratory of Experimental Gerontology, ² Laboratory of Neurosciences, ³ Molecular Dynamics Section, and ⁴ Laboratory of Immunology, Intramural Research Program, National Institute on Aging, Baltimore, Maryland

Requests for reprints: Donald K. Ingram, Laboratory of Experimental Gerontology, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224. Phone: 410-558-8180; Fax: 410-558-8604; E-mail: ingramd{at}grc.nia.nih.gov.

Background: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU).

Methods: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats.

Results: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP.

Conclusion: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP.

This article has been cited by other articles:

				J. Vardy, J. S. Wefel, T. Ahles, I. F. Tannock, and S. B. Schagen Cancer and cancer-therapy related cognitive dysfunction: an international perspective from the Venice cognitive workshop Ann. Onc., April 1, 2008; 19(4): 623 - 629. [Abstract] [Full Text] [PDF]

				A. B. Reiriz, G. K. Reolon, T. Preissler, J. O. Rosado, J. A. P. Henriques, R. Roesler, G. Schwartsmann, G. D. Lee, D. L. Longo, and D. K. Ingram Cancer Chemotherapy and Cognitive Function in Rodent Models: Memory Impairment Induced by Cyclophosphamide in Mice. Clin. Cancer Res., August 15, 2006; 12(16): 5000 - 5001. [Full Text] [PDF]