Evaluation of destructive effects of exposure to cisplatin during developmental stage: no profound evidence for sex differences in impaired motor and memory performance.
ABSTRACT We have elucidated the alteration in hippocampal and cerebellum function following chronic cisplatin treatment in male and female rats. Hippocampus and cerebellum related behavioral dysfunction in cisplatin-treated [intraperitoneally, 5 mg/(kg/week) for 5 weeks from 23-day-old] rats were analyzed using explorative, motor function, learning, and memory tasks (grasping, rotarod, open field, and Morris water maze tests). Exposure to cisplatin impaired the motor coordination in male and female rats. Exposure to cisplatin was reflected by a decrease in grasping time compared to vehicle-treated controls (saline) only in male rat while there were not any differences in female rats. When the rearing frequency, total distance moved and velocity of their recorded in open fieldtest, both males and females were dramatically affected by exposure to cisplatin. Compared to the saline, male and female rats trained 5 weeks after cisplatin injection showed significant memory deficits in the Morris water maze test. However, hippocampal and cerebellum functions of male and female rats were profoundly affected by exposure to cisplatin while no sex differences in the most variable were evident.
- Progress in Neurobiology 03/1994; 42(2):161-96. · 9.04 Impact Factor
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ABSTRACT: Neuroblastoma is a frequent pediatric tumor with a poor outcome in spite of aggressive treatment, even with autologous hematopoietic stem cell transplantation. The overall cure rate of 40% is unsatisfactory and new therapeutic strategies are urgently needed. AKT is a major mediator of survival signals that protect cells from apoptosis and regulate cell proliferation. The AKT signaling network is considered a key determinant of the biological aggressiveness of these tumors. In this article, the authors discuss the relation between activators of AKT in neuroblastoma, in particular, growth factors such as IGF-1, TRK, GDNF, VEGF and EGF, and their effects on tumoral proliferation, differentiation and apoptosis. Numerous other proteins interact with AKT in neuroblastoma. Several are relatively well characterized, such as PTEN and retinoic acid; others are new and potentially interesting, such as PKC and anaplastic lymphoma kinase. Specific inhibition of AKT has been studied, such as with LY249002, with significant effects on cell progression and apoptosis in tumoral cells. Moreover, a series of new drugs, such as geldanamycin and rapamycin, directly modify the expression of AKT in tumoral cells. Few specific inhibitors of AKT are available; less specific inhibitors are probably unsuitable therapeutic options in neuroblastoma. Drugs with a direct or indirect inhibitory effect on the AKT pathway, used alone or in combination with other drugs, seem to hold great promise as a new therapeutic modality in neuroblastoma.Expert Review of Anti-infective Therapy 06/2008; 8(5):757-69. · 2.07 Impact Factor
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ABSTRACT: Many cancer patients receiving chemotherapy experience fatigue, disturbed circadian rhythms, anorexia and a variety of dyspeptic symptoms including nausea. There is no animal model for this 'chemotherapy-related malaise' so we investigated the behavioural and molecular effects of a potent chemotherapeutic agent, cisplatin (CP, 6 mg/kg, i.p.) in rats. Dark-phase horizontal locomotor activity declined post-CP reaching a nadir on day 3 (P < 0.001), before recovering after 7 days. CP's effect was most marked in the late part (05.00-07.00) of the dark-phase. Food intake reached a nadir (P > 0.001) at 2 days, coincident with an increase in gastric contents (cisplatin 9.04+/-0.8 vs. saline 2.32+/-0.3 g; P < 0.001). No changes occurred in hypothalamic mRNA expression for AGRP, NPY, HCRT, CRH, IL-1, IL-6, TNFalpha, ABCG1, SLC6A4, PPIA and HPRT mRNA but tryptophan hydroxylase (TPH) mRNA was decreased (47%, P < 0.05) at day 21 post-CP. This shows that despite marked behavioural effects of cisplatin, only a discrete change (TPH) was found in hypothalamic mRNA expression and that occurred when the animals' behaviour had recovered. Findings are discussed in relation to the neuropharmacology of chemotherapy-induced malaise.Pharmacology Biochemistry and Behavior 01/2006; 83(1):9-20. · 2.61 Impact Factor