馬里蘭大學(xué)醫(yī)學(xué)院的研究人員利用珊瑚蟲(chóng)發(fā)出光芒的蛋白，點(diǎn)亮了在中樞神經(jīng)系統(tǒng)中發(fā)揮關(guān)鍵作用的腦細(xì)胞,。這種熒光標(biāo)記蛋白可幫助科學(xué)家了解與多種精神疾病有關(guān)的腦細(xì)胞缺陷,。研究結(jié)果刊登于2006年12月20日的Journal of Neuroscience中。
粒線體缺陷可能是阿茲海默癥,、帕金森氏癥以及中風(fēng)和衰老過(guò)程的一個(gè)環(huán)節(jié),。研究人員用這種標(biāo)記，區(qū)別神經(jīng)元的粒線體與神經(jīng)膠質(zhì)細(xì)胞的粒線體,。
研究小組負(fù)責(zé)人Krish Chandrasekaran副教授認(rèn)為,，這項(xiàng)新技術(shù)可以幫助研究人員解決許多問(wèn)題,，例如引起帕金森氏癥和阿茲海默癥之神經(jīng)元粒線體功能缺陷之程度如何,，也可以觀察神經(jīng)元粒線體是否會(huì)隨著年齡增長(zhǎng)而發(fā)生變化。
研究人員利用先進(jìn)的遺傳工程技術(shù),，制造出攜帶可鑒別神經(jīng)元粒線體之熒光蛋白的小鼠,。他們?cè)倮蔑@微鏡觀察這些小鼠的大腦，神經(jīng)元粒線體結(jié)構(gòu)會(huì)發(fā)出黃綠色光,。研究人員已經(jīng)證實(shí),，這些熒光蛋白的表現(xiàn)并不會(huì)影響神經(jīng)元粒線體的正常功能。
熒光標(biāo)記系統(tǒng)可用來(lái)探測(cè)神經(jīng)活動(dòng)方式,、粒線體能量制造系統(tǒng)的調(diào)節(jié)方式,，以及幫助研究人員了解二者間的交互作用。
(資料來(lái)源 : Bio.com)
英文原文摘要：
Neuron-Specific Conditional Expression of a Mitochondrially Targeted Fluorescent Protein in Mice
Krish Chandrasekaran, Julie L. Hazelton, Yu Wang, Gary Fiskum, and Tibor Kristian
Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland 21201
Correspondence should be addressed to either Krish Chandrasekaran or Tibor Kristian, Medical School Teaching Facility 5-34, 685 West Baltimore Street, Baltimore, MD 21201. Email: [email protected] or Email: [email protected]
Mitochondrial dysfunction contributes to the pathophysiology of both acute and chronic neurodegenerative disorders. Quantification of mitochondrial bioenergetic properties generally requires the use of isolated brain mitochondria. However, the involvement of neuronal mitochondrial dysfunction in these disorders is limited by the lack of markers, and therefore isolation procedures, that distinguish neuronal compared with astrocyte mitochondria. To address this and other issues concerning neuronal mitochondria in the CNS, transgenic mice were generated that express a fluorescent protein targeted specifically to neurons. A neuron-specific promoter, CaMKII (calcium/calmodulin-dependent kinase II) driven tTA (tetracycline transactivator) mice were crossed with TRE (tetracycline responsive element) driven mitochondrial targeted enhanced yellow fluorescent protein (eYFP) mice. Expression of eYFP in the bigenic mouse brain was observed only in neuronal mitochondria of striatum, forebrain, and hippocampus and was enhanced by the removal of the tetracycline analog doxycycline (Dox) in the diet. The respiratory control ratio of synaptic and nonsynaptic mitochondria isolated from eYFP-expressing mice was the same as control mice, suggesting that neuronal mitochondria expressing eYFP maintain normal bioenergetic functions. More importantly, the development of Dox-inducible, neuron targeted mito/eYFP transgenic mice offer a unique in vivo model for delineating the participation of neuronal mitochondria in neuronal survival and death.
Key words: cortex; hippocampus; neuron; mitochondria; transgenic; mice; eYFP; tetracycline; respiration; neurodegeneration; energy metabolism
Received Sept. 25, 2006; revised Nov. 14, 2006; accepted Nov. 14, 2006.
Correspondence should be addressed to either Krish Chandrasekaran or Tibor Kristian, Medical School Teaching Facility 5-34, 685 West Baltimore Street, Baltimore, MD 21201. Email: [email protected] or Email: [email protected]
