Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Unravelling Alzheimer's disease model via learning and memory function evaluation

S.Z. Raduan , Q.U. Ahmed , M.R.A. Rusmili , A.S.M. Sabere , M.S. Haris , M.F. Shaikh , W.A.W. Sulaiman , M.H. Mahmood
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Abstract

Introduction/objectives

Alzheimer's disease (AD) is characterised by a progressive decline in cognitive abilities, especially learning and memory. To validate the zebrafish as a suitable model organism for AD, the study examined the effects of 2 neurotoxin agents, aluminium chloride (AlCl3) and okadaic acid (OKA). In the full experimental design, both neurotoxins were administered intraperitoneally at 3 distinct doses (low, medium, and high) twice weekly for 21 days. At 3 time-points, behavioural tasks were conducted on day 7 (short duration), day 14 (moderate duration), and day 21 (long duration). The behavioural tasks consisted of a novel tank test lasting 6 min, followed by a T-maze tank test lasting 5 min.

Methods

In this article, the T-maze tank test was discussed in detail to evaluate which neurotoxins and their optimal dosages are impactful in developing a zebrafish AD model towards learning and memory functions. This evaluation measured four parameters: the amount of time spent in the wrong arm, the total distance travelled in the deeper chamber, and the 3-h and 24-h inflexion ratios.

Results

In summary, a 100 nM dosage of OKA with a maximum of 21 days of evaluation resulted in significant (P < .05) outcomes in all parameters evaluated. The longest duration was spent in the wrong arm, accompanied by a reduction in the total distance travelled in the deeper chamber and a decreasing pattern in the 3-h and 24-h inflexion ratios.

Conclusion

These observations suggest that OKA is the optimal choice of neurotoxin for a validated and optimised zebrafish AD model.
氯化铝和冈田酸对斑马鱼的神经毒性:通过学习和记忆功能评估揭示阿尔茨海默病模型
引言/目的阿尔茨海默病(AD)的特征是认知能力逐渐下降,尤其是学习和记忆能力。为了验证斑马鱼是否适合作为老年痴呆症的模型生物,本研究考察了氯化铝(AlCl3)和冈田酸(OKA)这两种神经毒素的影响。在完整的实验设计中,两种神经毒素均以3种不同的剂量(低、中、高)腹腔注射,每周两次,共21天。在3个时间点,分别于第7天(持续时间短)、第14天(持续时间中等)和第21天(持续时间长)进行行为任务。本文详细讨论了 T 型迷宫水箱试验,以评估哪些神经毒素及其最佳剂量对开发斑马鱼 AD 模型的学习和记忆功能有影响。该评估测量了四个参数:花在错误手臂上的时间、在更深的迷宫中行进的总距离以及 3 小时和 24 小时的拐点比率。结果总之,100 nM 剂量的 OKA 和最长 21 天的评估结果在所有评估参数中都具有显著性(P < .05)。在错误臂中停留的时间最长,同时在深腔中的总行程减少,3 小时和 24 小时的屈伸比呈下降趋势。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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