Fruit ripening retardant Daminozide induces cognitive impairment, cell specific neurotoxicity, and genotoxicity in Drosophila melanogaster

IF 3.4 3区 医学 Q2 NEUROSCIENCES Neurotoxicology Pub Date : 2024-06-06 DOI:10.1016/j.neuro.2024.06.002
Debasmita Das , Gaurab Ghosh , Arthita Dutta , Rinchen D. Sherpa , Papiya Ghosh , Subhra Prakash Hui , Sujay Ghosh
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Abstract

Background

We explored neurotoxic and genotoxic effects of Daminozide, a fruit ripening retardant, on the brain of Drosophila melanogaster, based on our previous finding of DNA fragmentation in larval brain cell in the flies experimentally exposed to this chemicals.

Methods

Adult flies were subjected to two distinct concentrations of daminozide (200 mg/L and 400 mg/L) mixed in culture medium, followed by an examination of specific behaviors such as courtship conditioning and aversive phototaxis, which serve as indicators of cognitive functions. We investigated brain histology and histochemistry to assess the overall toxicity of daminozide, focusing on neuron type-specific effects. Additionally, we conducted studies on gene expression specific to neuronal function. Statistical comparisons were then made between the exposed and control flies across all tested attributes.

Results

The outcome of behavioral assays suggested deleterious effects of Daminozide on learning, short term and long term memory function. Histological examination of brain sections revealed cellular degeneration, within Kenyon cell neuropiles in Daminozide-exposed flies. Neurone specific Immuno-histochemistry study revealed significant reduction of dopaminergic and glutaminergic neurones with discernible reduction in cellular counts, alteration in cell and nuclear morphology among daminozide exposed flies. Gene expression analyses demonstrated upregulation of rutabaga (rut), hb9 and down regulation of PKa- C1, CrebB, Ace and nAchRbeta-1 in exposed flies which suggest dysregulation of gene functions involved in motor neuron activity, learning, and memory.

Conclusion

Taken together, our findings suggests that Daminozide induces multifaceted harmful impacts on the neural terrain of Drosophila melanogaster, posing a threat to its cognitive abilities.

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果实催熟剂达米诺酰胺会诱发黑腹果蝇的认知障碍、细胞特异性神经毒性和遗传毒性。
背景:根据我们之前在实验中发现的暴露于达米诺酰胺(一种水果成熟延缓剂)的果蝇幼虫脑细胞的 DNA 断裂现象,我们探讨了达米诺酰胺对黑腹果蝇大脑的神经毒性和基因毒性影响:方法:将两种不同浓度的达米诺肼(200毫克/升和400毫克/升)混合在培养基中,对成年果蝇进行实验,然后检测其特定行为,如求偶条件反射和厌恶性趋光性,这些行为可作为认知功能的指标。我们对脑组织学和组织化学进行了研究,以评估达米诺嗪的整体毒性,重点关注神经元类型的特异性影响。此外,我们还对神经元功能的特定基因表达进行了研究。然后对暴露蝇和对照蝇的所有测试属性进行了统计比较:行为测定结果表明,达米诺嗪对学习、短期和长期记忆功能有有害影响。脑切片的组织学检查显示,暴露于达米诺嗪的苍蝇的凯尼恩细胞神经节发生了细胞变性。神经元特异性免疫组织化学研究显示,暴露于达米诺嗪的苍蝇体内多巴胺能神经元和谷氨酸能神经元显著减少,细胞数量明显减少,细胞和细胞核形态发生改变。基因表达分析表明,暴露于达米诺嗪的苍蝇中,芦竹(rut)和 hb9 上调,PKa- C1、CrebB、Ace 和 nAchRbeta-1 下调,这表明涉及运动神经元活动、学习和记忆的基因功能失调:综上所述,我们的研究结果表明,达米诺嗪会对黑腹果蝇的神经系统产生多方面的有害影响,对其认知能力构成威胁。
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来源期刊
Neurotoxicology
Neurotoxicology 医学-毒理学
CiteScore
6.80
自引率
5.90%
发文量
161
审稿时长
70 days
期刊介绍: NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.
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