Effect of the knockdown of amyloid precursor protein on intracellular calcium increases in a neuronal cell line derived from the cerebral cortex of a trisomy 16 mouse

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• 作者：Guillermo Rojas ; Ana Marí ; a Cá ; rdenas ; Paola Ferná ; ndez-Olivares ; Takeshi Shimahara ; Juan Segura-Aguilar ; Raú ; l Caviedes ; Pablo Caviedes
• 关键词：Calcium ; Glutamate ; Nicotine ; Antisense ; Down syndrome
• 刊名：Experimental Neurology
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：209
• 期：1
• 页码：234-242
• 全文大小：570 K

文摘

Murine trisomy 16 (Ts16) is a useful model to study the deleterious effect of aneuploidy in neural pathophysiology. The CTb cell line derived from the cerebral cortex of a Ts16 mouse overexpresses the amyloid precursor protein (APP) and exhibits altered intracellular Ca²⁺ homeostasis. In the present work, we induced knockdown of APP by transfecting specific mRNA antisense sequences into CTb cells. Forty-eight hours after transfection, the APP expression was knocked down by 40 % , reaching levels comparable to those of the cortical line CNh, derived from a normal animal. Calcium measurements showed that the APP knockdown decreased intracellular Ca²⁺ basal levels and accelerated the kinetics of the decay of Ca²⁺ responses induced by glutamatergic agonists, nicotine, depolarization or ionomycin, to levels similar to those previously reported for CNh cells. The present results suggest that APP overexpression plays an important role on the altered intracellular Ca²⁺ homeostasis in the trisomic cells.