Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration
Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration
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DOI：
10.3390/cells9081883
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发表时间：
2020-08-01
期刊：
影响因子：
6
通讯作者：
Pendyala, Gurudutt
中科院分区：
文献类型：
--
作者：
Koul, Sneh;Schaal, Victoria L.;Pendyala, Gurudutt
在美国，吸烟仍然是一个重大的健康和经济问题。此外，两性之间尼古丁摄入量的新模式进一步增加了一层复杂性。尼古丁是一种强效精神兴奋剂，具有高度成瘾倾向，可显著改变大脑功能。然而，尼古丁对大脑功能和行为影响的神经生物学机制仍不清楚。阐明这些机制具有很高的临床意义，并可能导致改善戒烟治疗。为了填补这一关键的知识空白，我们目前的研究重点是识别尼古丁自我给药后雄性和雌性大鼠中性别特异性脑源性细胞外囊泡（BDEV）特征。细胞外囊泡（EV）基于其来源或大小由磷脂纳米囊泡如凋亡小体、微囊泡（MV）和外来体组成。EV作为参与细胞-细胞通讯的分子，从而调节几种疾病的病理生理学，引起了人们的极大关注。有趣的是，与男性相比，尼古丁自我给药后的女性显示出更大的BDEV大小，沿着EV生物发生受损。接下来，使用基于定量质谱的蛋白质组学，我们确定了BDEV特征，包括不同的分子途径，影响男性和女性之间。总之，本研究确定了与长期尼古丁自我给药相关的BDEV生物发生、蛋白质货物特征和分子途径的性别特异性变化。
Smoking remains a significant health and economic concern in the United States. Furthermore, the emerging pattern of nicotine intake between sexes further adds a layer of complexity. Nicotine is a potent psychostimulant with a high addiction liability that can significantly alter brain function. However, the neurobiological mechanisms underlying nicotine's impact on brain function and behavior remain unclear. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation. To fill in this critical knowledge gap, our current study focused on identifying sex-specific brain-derived extracellular vesicles (BDEV) signatures in male and female rats post nicotine self-administration. Extracellular vesicles (EVs) are comprised of phospholipid nanovesicles such as apoptotic bodies, microvesicles (MVs), and exosomes based on their origin or size. EVs are garnering significant attention as molecules involved in cell-cell communication and thus regulating the pathophysiology of several diseases. Interestingly, females post nicotine self-administration, showed larger BDEV sizes, along with impaired EV biogenesis compared to males. Next, using quantitative mass spectrometry-based proteomics, we identified BDEV signatures, including distinct molecular pathways, impacted between males and females. In summary, this study has identified sex-specific changes in BDEV biogenesis, protein cargo signatures, and molecular pathways associated with long-term nicotine self-administration.