Autism Linked to Zinc Deficiency in Childhood 自閉癥與兒時缺鋅有關

阿里斯托斯·喬治烏文 劉偉譯

While the exact cause of autism is unknown， its development in children has been linked to various genetic and environmental factors—including zinc deficiency.

It is still not clear whether this deficiency contributes to autism， but scientists have defined a possible mechanism for how this could work， according to a paper published in Frontiers in Molecular Neuroscience. For their study， the researchers demonstrated how zinc shapes the connections， or synapses， between brain cells （neurons） that form during early development via a complex molecular machinery controlled by autism-linked genes.

“Autism is associated with specific variants of genes involved in the formation， maturation and stabilization of synapses during early development，” Sally Kim， lead author of the study from Stanford University School of Medicine， said in a statement.

“Our findings link zinc levels in neurons—via interactions with the proteins encoded by these genes—to the development of autism，” Kim said.

The team found that when a brain signal was transferred via a synapse， zinc entered the target neuron where it could bind two of these proteins， known as SHANK2 and SHANK3. Those proteins cause changes in the composition and function of adjacent signal receptors， called AMPARs， on the neurons surface at the synapse.

The finding that zinc shapes the properties of developing synapses via SHANK proteins suggests that a lack of the mineral during early development could potentially contribute to autism by impairing the function of synapses， which enable brain cells to communicate with one another.

“Understanding the interaction between zinc and SHANK proteins could therefore lead to diagnostic， treatment and prevention strategies for autism，” suggested John Huguenard， co-senior author of the study， of Stanford University School of Medicine.

Its important to note， however， that at present it isnt possible to make any concrete conclusions or begin recommending that children take zinc supplements.

“Currently there are no controlled studies of autism risk with zinc supplementation in pregnant women or babies， so the jury is still out1，” Craig Garner， co-author of the study from the German Centre for Neurodegenerative Diseases， said. “But experimental work in autism models also published in this Frontiers Research Topic holds promise.”

Taking too much zinc can reduce the amount of copper the body absorbs， which can result in anemia and weakening of bones. Furthermore， zinc deficiency does not necessarily imply a dietary deficiency， and could be caused by problems with absorption in the gut， for example.

“Nevertheless， our findings offer a novel mechanism for understanding how zinc deficiency—or disrupted handling of zinc in neurons—might contribute to autism，” Garner said.

Autism is a lifelong developmental disability that affects how people perceive the world and interact with others. The autism spectrum contains a range of similar disorders， such as Aspergers syndrome.

盡管自閉癥的確切原因不明，但目前已發現，兒童患上此病與各種遺傳和環境因素有關，其中包括缺鋅。

根據《分子神經科學前言》期刊發表的論文，雖然現在仍不清楚缺鋅是否會導致自閉癥，但科學家指明了它產生這種影響的可能作用機制。在其研究中，研究者證明了鋅如何通過自閉癥相關基因控制的復雜分子機制，來影響早期發育過程中形成的腦細胞（神經元）連接，或者說突觸。

“自閉癥與特定的基因變異有關，這些基因影響早期發育過程中突觸的形成、成熟和穩定。”該研究論文的第一作者、斯坦福大學醫學院的薩莉·金在一份聲明中如是說。

金說：“我們的研究結果表明，通過與這些基因編碼形成的蛋白質相互作用，神經元中的鋅含量會導致自閉癥。”

研究團隊發現，突觸傳遞大腦信號時，鋅就進入目標神經元，在那里將SHANK2和SHANK3這兩種蛋白質結合起來。這些蛋白質會導致突觸神經元表面相鄰信號受體（名為α-氨基-3-羥基-5-甲基-4-異唑受體）的成分和功能發生改變。

鋅會通過SHANK蛋白質改變發育中的突觸特性，這一研究結果表明，早期發育過程中，缺鋅會損害突觸使腦細胞能夠彼此交流的功能，可能導致自閉癥。

該研究論文的另一主要作者、斯坦福大學醫學院的約翰·于格納爾認為：“了解鋅和SHANK蛋白之間的相互作用就能找到自閉癥的診斷、治療和預防措施。”

然而，需要特別注意的是，目前無法做出任何具體的結論或者開始建議兒童補鋅。

“當下沒有針對孕婦或嬰幼補鋅對自閉癥風險影響的對照研究，所以，現在仍無定論。”該研究論文的另一位作者、德國神經退行性疾病中心的克雷格·加納說，“但是同樣發表在這一‘前沿研究課題專欄中的自閉癥模型實驗研究前景樂觀。”

鋅攝入過多會降低身體對銅的吸收，導致貧血和骨質疏松。此外，缺鋅不一定意味著飲食營養缺乏，比如它還可能由腸道吸收問題所致。

加納說：“不過，我們的研究成果提供了一種新機制來了解缺鋅（或者說鋅在神經元中的運作受到干擾）何以可能導致自閉癥。”

自閉癥是一種終身的發育障礙，影響人們對世界的感知，以及和他人的互動。自閉癥譜系障礙包含一系列類似的疾病，比如阿斯佩格綜合征。

1 the jury is （still） out on sth〈俚語〉（某事）仍未定奪，懸而未決。