Neurological disorders often have sex biases, and these differences could be due to altered protein expression in the brain.
神經系統疾病通常具有性別趨勢，而此些差異可能是由於大腦中，經改變的蛋白質表現。
Many neurological and psychiatric conditions differ in their prevalence and risk based on biological sex. “There is a sort of dearth of understanding of how biologic sex influences traits,” said Thomas Wingo, a neurologist at Emory University.
諸多神經系統及精神疾病，在其盛行率與風險上，基於生物性別而異。美國埃默里大學神經學家，Thomas Wingo宣稱：「目前缺乏，有關生物性別如何影響特性的瞭解。」
Wingo and his team investigated this problem and showed that sex influences gene and protein expression in the brain. The findings, published in Nature Medicine, are a first step toward mechanistically understanding why some neurological conditions have pronounced sex-biases, which could guide improved treatments.
Wingo及其團隊調查研究了，此問題且證實了，性別影響大腦中之基因及蛋白質的表現。此些發表於《自然•醫學》期刊的研究發現，是邁向機制上瞭解，為何某些神經系統疾病，具有明顯性別趨勢的第一步。這可能引領出，諸多改善的治療法。
The team used donated post-mortem brain samples from individuals over the age of 60 with and without neurologic conditions. Using mass spectrometry, the researchers studied the proteome in six brain regions from more than 1,200 brains.
該團隊使用了，來自60歲以上，患有或不患有神經系統疾病者，捐贈之死後的大腦樣本。使用質譜分析法，此些研究人員研究了，來自於1200多個大腦之6個大腦區域的蛋白質體。
After quality control analysis, the team evaluated just under 10,200 proteins for sex-based differences. More than 1,300 of these proteins exhibited different expression levels based on sex.
在質量控制分析後，對基於性別的差異，該團隊評估了，近10200種蛋白質。其中1300種蛋白質，根據性別展現了不同的表現程度。
“The study stands out because it has a very big sample [size],” noted Christina Dalla, a neuropsychopharmocologist at the National and Kapodistrian University of Athens, who was not involved in the study.
希臘雅典國立卡波季斯特里亞大學，未參與該項研究的神經精神藥理學家，Christina Dalla特別指出：「該項研究引人注目，因為它具有非常大的樣本數量。」
To investigate potential differences in genetic regulation based on sex, the team analyzed gene variants for their influence on protein expression levels, or protein quantitative trait loci (pQTL).
為了調查研究，基於性別之遺傳調節的潛在差異。該團隊分析了，有關基因變異對蛋白質表現程度，或蛋白質數量特性位點(pQTL)的影響。
They focused this analysis on the dorsolateral prefrontal cortex as it was highly represented in their sample and therefore provided robust proteomic and genetic data. They assessed protein expression between alleles with single nucleotide polymorphisms and looked for pQTL differences to determine if sex influenced this allele expression.
他們將此分析著重於，大腦背外側前額葉皮質上。因為，它在他們的樣本中，具有很高的代表性。因此，提供了堅定之蛋白質體及遺傳的數據。他們評估了，具有單核苷酸多態性之等位基因間的蛋白質表現，並尋找了pQTL差異，以確定性別是否影響了，該等位基因表現。
“The natural hypothesis is, they’re probably pretty similar,” said Thomas Wingo. “Generally, that’s not what we saw.” The researchers found almost 1,200 loci that corresponded to about 150 proteins with sex-biased expression.
Thomas Wingo宣稱：「合乎道理的假設是，它們可能非常相似。大體上，那不是我們所看到的。」此些研究人員發現了，近1200個對應於大約150種，具有性別趨勢之表現的蛋白質位點(基因座)。
“Looking at brain proteins and genetic regulation of brain proteins would be a great window into the mechanisms of these neuropsychiatric disorders,” said Aliza Wingo, a psychiatrist at Emory University and study coauthor.
該項研究合撰人，埃默里大學的精神病學家，Aliza Wingo宣稱：「探究大腦蛋白質及大腦蛋白質的基因調節，會是瞭解此些神經精神疾病機制的一個重要窗口。」
Because several brain conditions exhibit sex biases, the researchers compared the identified sex-biased proteins and their genes to gene-protein pairs that they previously associated with causal roles in a set of psychiatric, neurologic, or morphologic traits.
由於幾種大腦疾病展現出性別趨勢，此些研究人員進行了，已經被確認之性別趨勢的蛋白質及其基因與之前它們，在一系列精神病學、神經學或形態學特性中，與具因果角色有所關聯之基因-蛋白質對的比較。
The team identified 35 proteins from this group with sex-biased expression. Dalla noted that a strength of the present study was that it did not focus on a single disorder. “It really makes it unique that it manages to investigate so many different causal genes and proteins,” she said.
該團隊從這群中，確認了35種具有性別趨勢之表現的蛋白質。Dalla特別指出，目前該項研究的一種優勢是，它並非著重於單一疾病。她宣稱：「這確實使其獨特。因為，它設法調查研究了，很多不同之具有因果關係的基因及蛋白質。」
Aliza Wingo explained that this is only the beginning for this work. “I believe that we can find more [sex-biased risk genes] when we have access to more sex-stratified genome wide association studies because, right now, those are limited,” she said, adding that more data could improve the design of therapeutic interventions.
Aliza Wingo解釋，這只是該項研究的開始。她宣稱：「我相信，當我們有更多性別分層之基因體廣泛關聯的研究途徑(因為，目前那些是有限的)時，我們能找到更多性別趨勢的風險基因。」補充說，更多的數據可能改善，治療介入的設計。
The team anticipates that factors such as the environment can influence brain protein expression between sexes, but they are excited about their current findings.
該團隊預期，諸如環境等因素，會影響在性別之間的大腦蛋白質表現。不過，有關其目前的此些研究發現，他們是興奮的。
“The fact that we are able to detect things that are changing or different between the brain that are relevant to these outcomes may start to help us understand why there’s prevalence differences for these traits,” said Thomas Wingo. “That’s an interesting new avenue to explore.”
Thomas Wingo宣稱：「我們能探究出，在與此些結果有關聯的大腦間，正在改變或不同之事物的事實，可能開始有助於我們，瞭解為何此些特性，有廣泛差異。那是一種，令人感興趣的新探索途徑。」
網址：https://www.the-scientist.com/biological-sex-influences-brain-protein-expression-71763
翻譯：許東榮
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