The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory

Author(s)

Wasilewska-Sampaio, Ana Paula ^[1] ; Santos, Tiago G. ^[1] ; Lopes, Marilene Hohmuth ^[2] ; Cammarota, Martin ^[3] ; Martins, Vilma Regina ^{[1, 4, 5]}

Affiliation

^[1] AC Camargo Canc Ctr, Int Res Ctr, BR-01508010 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil

^[3] Univ Fed Rio Grande do Norte, Inst Brain, BR-59056450 Natal, RN - Brazil

^[4] Natl Inst Translat Neurosci, BR-01508010 Sao Paulo - Brazil

^[5] CNPq MCT, Natl Inst Oncogen, BR-01508010 Sao Paulo - Brazil

• Document type: Journal article
• Source: Physiology & Behavior; v. 123, p. 55-61, JAN 17 2014.
• Web of Science Citations: 4

Abstract

Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18 days (D9. D14, and 018, respectively) after implantation of 5 x 10(5) cells. At 09, the mice showed normal behavior when tested 90 min or 24 h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24 days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches
• Grantee: Vilma Regina Martins
• Support Opportunities: Research Projects - Thematic Grants