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HKUST Unravels Molecular Mechanism Behind Autism and Neurodevelopmental Disorders

香港科技大學首次成功解開特定蛋白與調控大腦發育新機理 有助了解自閉症相關疾病

    Neuron

Axin directs the amplification and differentiation of intermediate progenitors in the developing cerebral cortex

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    - Video Abstract

 

    South China Morning Post

HKUST brain study offers hope for treating autism

Researchers at University of Science and Technology have made a breakthrough in the study of the brain, with potential implications for the treatment of conditions such as autism and Parkinson's disease.

Led by the university's Dean of Science Professor Nancy Ip, the team of neuroscientists demonstrated that the size of the brain's cerebral cortex - which controls mental functions such as language, consciousness and abstract thought - can be expanded by increasing production of the brains' neurons.

The team identified a protein, Axin, that plays a key role in the production of neurons and which can be increased by specific chemicals.

Although the researchers are testing only on mice, they believe the discovery will be applicable to stem-cell therapy and that they will be able to test whether developmental disorders can be treated by varying the number of neurons in the brain.

Developmental disorders can be caused by the brain having an abnormal number of neurons when it is formed.

Recent scientific evidence suggests autism is strongly associated with overproduction of neurons. The study showed the increased production of neurons was associated with autistic behaviour in mice.

According to Ip, the discovery is also relevant to people suffering from Parkinson's disease, a degenerative disorder of the central nervous system.

"Understanding the mechanism that controls the production of brain cells also has relevance to other diseases, for example neuro-degenerative diseases such as Parkinson's," she said. "It is because there is a loss of neurons, so you want to generate more neurons in this case.

"[In that case], we could manipulate the Axin pathway so that if we activate it, it will result in an increased number of neurons."

The team hopes to test the theory on humans in 10 years and eventually manufacture drugs to control the level of neurons.

    蘋果日報

Axin蛋白令大腦皮層變厚  科大揪出自閉症真兇

自閉症困擾不少家長,科大科學家證實基因影響大腦皮層的成長,在小鼠身上成功發現Axin蛋白能影響「中間前體細胞」,從而決定大腦的體積。在研究中,20隻受Axin刺激的小鼠,其中約9成老鼠出現自閉症的行為,例如逃避其他老鼠等。研究員指現時已找到自閉症「真兇」,下一步可研發新藥。

每90名兒童就有一人患有自閉症,科學家雖已知道自閉症患者的大腦皮層較普通人為厚,但一直未找到令皮層變厚的成因。 科大理學院院長葉玉如及其研究團隊,約三年前針對大腦皮層變厚的問題,探究與基因關係。負責研究的生命科學部副研究員方偉群,在3年前因研究Axin蛋白在癌症的角色中,發現對大腦皮層有影響,故轉變研究Axin蛋白對自閉症的影響。

9成受注射鼠性格固執

方偉群指,在人類24對基因中,排第16的基因蛋白Axin能影響神經細胞數量,會影響皮層厚薄及控制大腦體積,過去三年在逾百隻小鼠身上做實驗。 由於出生後的小老鼠大腦已發育,故研究員在母體中的幼鼠入手。幼鼠在母體中第13天(等同人類胚胎成長至兩至三個月)接受注射,研究員在小鼠的腦腔,注入防止Axin蛋白溶解的物質,小鼠在5日後出生,研究員發現Axin蛋白刺激皮層細胞,受注射的小鼠腦細胞較一般小鼠多五至八成,即皮層較厚。

20隻受注射的小鼠發育和普通鼠一樣,但約9成小鼠出現重複自我清潔行為,社交上逃避陌生老鼠,性格固執,堅持埋藏所有波子等,類似一般的自閉症行為。

葉玉如指,今次研究發現Axin蛋白的角色,如同生物標籤(bio-marker),有助日後研發幹細胞療法,令皮層改變厚薄。對於腦細胞不足的疾病如腦退化症,Axin蛋白有助刺激腦幹細胞增長,理論上有望治療腦退化症。

葉玉如認為胎兒在母體神經細胞已發育成長,故在懷孕期介入治療較為有效,但強調現仍在基礎研究階段,未能在人類身上應用。Axin蛋白對大腦的影響研究報告已刊登在權威科學期刊《Neuron》。

    東方日報

 

自閉症或與腦部蛋白含量有關

大多自閉症患者有社交障礙,科學家早知與大腦體積過大及神經細胞過多有關,但未知哪種物質「作怪」。香港科技大學首度發現,哺乳類動物體內有某種蛋白,控制腦神經細胞生長。研究員透過干擾老鼠胚胎腦部的特定蛋白含量,令老鼠大腦皮層變厚,神經細胞數目增加五成至八成,成年老鼠其後重複自我清潔毛髮,不願與陌生老鼠接觸,變成「自閉老鼠」。研究成果有助發展自閉症、智力發展遲緩等腦部疾病的新治療。

科大用老鼠研究有突破

科大理學院院長葉玉如領導的四人研究小組進行歷時三年研究,先在一百至二百隻已發育十三日的老鼠胚胎大腦注入化學物質,阻止名叫「Axin」的蛋白被分解。

老鼠胚胎出生後,研究員解剖其腦部及掃描腦部結構,發現老鼠大腦皮層加厚,神經細胞較一般老鼠多五成至八成。

葉玉如解釋,Axin蛋白會控制腦幹細胞「中間前體細胞」形成神經細胞,從而決定大腦體積,現已有研究指神經細胞過多會導致部分人出現自閉症,細胞多寡亦與巨腦症、小腦症及精神病有關,相信有助科學家研究新幹細胞療法、藥物治療新方向,惟能否在人腦注射某物質令細胞數目回復正常,甚至令病情逆轉仍言之尚早。研究已於神經科學權威期刊《神經元》發表。

參與研究的科大生命科學部副研究員方偉群表示,長期觀察二十隻被干擾Axin蛋白的老鼠,發覺當中十八隻與一般老鼠行為有異,包括不斷重複舔自己的身體清潔,又不似一般老鼠會與陌生老鼠接觸,猶如「自閉」,顯示牠們有溝通障礙。下階段會研究神經細胞達哪種程度才致老鼠有自閉症行為問題。

 
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