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抑制外核苷酸酶和腺苷脱氨酶能够逆转斑马鱼(Danio rerio)早期乙醇暴露的长期行为影响。

Inhibition of ecto-5'-nucleotidase and adenosine deaminase is able to reverse long-term behavioural effects of early ethanol exposure in zebrafish (Danio rerio).

机构信息

Laboratório de Neuroquímica E Psicofarmacologia, Escola de Ciências da Saúde E da Vida, Pontifícia Universidade Católica Do Rio Grande Do Sul, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.

出版信息

Sci Rep. 2020 Oct 20;10(1):17809. doi: 10.1038/s41598-020-74832-0.

DOI:10.1038/s41598-020-74832-0
PMID:33082435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7576130/
Abstract

The behavioural impacts of prenatal exposure to ethanol include a lower IQ, learning problems, anxiety and conduct disorders. Several components of the neurochemical network could contribute to the long-lasting effects of ethanol embryonic exposure. Adenosine is an important neuromodulator, that has been indicated to be affected by acute and chronic exposure to ethanol. Here, embryos of zebrafish exposed to 1% ethanol during the developmental stages of gastrula/segmentation or pharyngula exhibited anxiolytic effect, increased aggressiveness, and decreased social interaction. The exposure during pharyngula stage was able to affect all behavioural parameters analysed at 3 months-post fertilization (mpf), while the treatment during gastrula stage affected the anxiety and social interaction parameters. The aggressiveness was the only behavioural effect of early ethanol exposure that lasted to 12 mpf. The use of a specific inhibitor of adenosine production, the inhibitor of ecto-5'-nucleotidase (AMPCP/150 mg/kg), and the specific inhibitor of adenosine degradation, the inhibitor of adenosine deaminase, EHNA (100 mg/kg) did not affect the effects over anxiety. However, AMPCP at 3 mpf, but not EHNA, reversed aggressive parameters. AMPCP also recovered the social interaction parameter at 3 mpf in animals treated in both stages, while EHNA recovered this parameter just in those animals treated with ethanol during the gastrula stage. These results suggest that long-lasting behavioural effects of ethanol can be modulated by intervention on ecto-5'-nucleotidase and adenosine deaminase activities.

摘要

产前暴露于乙醇的行为影响包括智商降低、学习问题、焦虑和行为障碍。神经化学网络的几个组成部分可能导致乙醇胚胎暴露的持久影响。腺苷是一种重要的神经调质,已表明其受到急性和慢性乙醇暴露的影响。在这里,在原肠胚/体节或咽胚发育阶段暴露于 1%乙醇的斑马鱼胚胎表现出焦虑缓解作用、攻击性增加和社交互动减少。在咽胚阶段的暴露能够影响在受精后 3 个月(mpf)分析的所有行为参数,而在原肠胚阶段的处理影响焦虑和社交互动参数。攻击性是早期乙醇暴露唯一持续到 12 mpf 的行为效应。使用特定的腺苷产生抑制剂,外核苷酸酶的抑制剂(AMPCP/150mg/kg)和腺苷降解的特异性抑制剂,腺苷脱氨酶抑制剂 EHNA(100mg/kg),不会影响焦虑作用。然而,在 3 mpf 时 AMPCP 而非 EHNA 逆转了攻击性参数。AMPCP 还在两个阶段都接受治疗的动物中恢复了 3 mpf 的社交互动参数,而 EHNA 仅在那些在原肠胚阶段接受乙醇治疗的动物中恢复了该参数。这些结果表明,乙醇的持久行为影响可以通过对外核苷酸酶和腺苷脱氨酶活性的干预来调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/f7a3498d7246/41598_2020_74832_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/17f34ead3609/41598_2020_74832_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/1e46fad4ab20/41598_2020_74832_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/bbeb4f9e412a/41598_2020_74832_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/37230310a394/41598_2020_74832_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/f7a3498d7246/41598_2020_74832_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/17f34ead3609/41598_2020_74832_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/1e46fad4ab20/41598_2020_74832_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/bbeb4f9e412a/41598_2020_74832_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/37230310a394/41598_2020_74832_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1290/7576130/f7a3498d7246/41598_2020_74832_Fig5_HTML.jpg

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