کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2595965 1562364 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cytarabine induced cerebellar neuronal damage in juvenile rat: Correlating neurobehavioral performance with cellular and genetic alterations
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Cytarabine induced cerebellar neuronal damage in juvenile rat: Correlating neurobehavioral performance with cellular and genetic alterations
چکیده انگلیسی

Cytosine arabinoside (Ara-C), a pyrimidine analogue induces cerebellar dysfunction and behavioral abnormalities. Although many in vitro experiments have been conducted in the past demonstrating the lethal potential of Ara-C to cerebellar neurons, there is a paucity of literature available regarding the effects of Ara-C on the cellular and genetic material of cerebellum and its subsequent influence on the neurobehavioral performance in vivo. Rats were treated with Ara-C at the dose levels 50, 100 and 200 mg/kg/day for 5 and 14 days by intraperitoneal (i.p.) route. Endpoints of the evaluation included food and water intake, body and organ weight, behavioral parameters, histopathology, oxidative stress, DNA damage, apoptosis, expression of p53, caspase-3 and calbindin D-28K (calbindin) as well as histone acetylation and methylation. Ara-C treatment for 14 days significantly decreased the food and water intake, body weight gain and brain weight in rat as compared to the control. Alterations in various behavioral parameters were observed, indicating the impaired cerebellar function. Further, cellular abnormalities in the cerebellum such as Purkinje cell misalignment and granule cell cytotoxicity were observed. Positive correlation was observed between Ara-C induced disturbance in the motor performance and the Purkinje cell loss in rat cerebellum. Moreover, Ara-C treatment significantly increased the oxidative stress, DNA damage, TUNEL positive cells, p53 and caspase-3 positive cells in the rat cerebellum. Unlike short-term treatment, long-term Ara-C treatment significantly reduced calbindin expression in the cerebellum. Apart from this, 14 days Ara-C treatment led to significant alterations in the histone acetylation and methylation in the cerebellum, while in 5 days treatment no such alterations were observed. Present results indicated that Ara-C, by inducing oxidative stress mediated DNA damage, executes neuronal apoptosis which is accompanied by an increase in the p53 and caspase-3, but decrease in the calbindin expression.


► Ara-C induces behavioral alterations in rats that indicate cerebellar dysfunction.
► Ara-C induces oxidative stress mediated DNA damage in cerebellar neurons.
► Ara-C utilizes p53 and caspase-3 dependent pathway to induce neuronal apoptosis.
► Ara-C induces significant alterations in histone H3 acetylation and monomethylation.
► Long-term Ara-C treatment down-regulates calbindin level in the Purkinje cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 293, Issues 1–3, 11 March 2012, Pages 41–52
نویسندگان
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