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Real-Time Neuroimaging Technology Offers Glimpse Inside the Cell

By MedImaging International staff writers
Posted on 08 May 2014
Image: The micrograph shows a peripheral nerve, with the neuromuscular endplates stained in red. The nerve-cell mitochondria were imaged with a fluorescent redox sensor (green in the cytoplasm, yellow at the endplates) (Photo courtesy of M. Kerschensteiner and T. Misgeld).
Image: The micrograph shows a peripheral nerve, with the neuromuscular endplates stained in red. The nerve-cell mitochondria were imaged with a fluorescent redox sensor (green in the cytoplasm, yellow at the endplates) (Photo courtesy of M. Kerschensteiner and T. Misgeld).
Cutting-edge imaging technology provides insights into the role of redox signaling and reactive oxygen species in living neurons, in real time. German scientists have developed a new optical microscopy technique that provides insights into the role of oxidative stress in damaged as well as healthy nervous systems.

The study, performed by researchers from Technische Universität München (TUM; Germany) and the Ludwig-Maximilians-Universität München (LMU; Germany), was described in the April 2014 issue of the journal Nature Medicine.

Reactive oxygen species (ROS) are important intracellular signaling molecules, but their course of action is complicated: In low concentrations they control key aspects of cellular function and behavior, while at high concentrations they can cause oxidative stress, which damages DNA, organelles, and membranes. To examine how redox signaling unfolds in single cells and organelles in real-time, an innovative optical microscopy technique has been developed cooperatively by the teams of LMU Prof. Martin Kerschensteiner and TUM Prof. Thomas Misgeld, both investigators of the Munich Cluster for Systems Neurology (SyNergy).

“Our new optical approach allows us to visualize the redox state of important cellular organelles, mitochondria, in real time in living tissue,” Prof. Kerschensteiner said. In earlier studies, the investigators had obtained validation that oxidative damage of mitochondria might contribute to the destruction of axons in inflammatory diseases such as multiple sclerosis.

The new technology allows the scientists to monitor the oxidation states of individual mitochondria with high spatial and temporal resolution. Prof. Kerschensteiner explained the incentive behind the development of the technique. “Redox signals have important physiological functions, but can also cause damage, for example when present in high concentrations around immune cells.”

The scientists used redox-sensitive variants of the green fluorescent protein (GFP) as visualization tools. “By combining these with other biosensors and vital dyes, we were able to establish an approach that permits us to simultaneously monitor redox signals together with mitochondrial calcium currents, as well as changes in the electrical potential and the proton (pH) gradient across the mitochondrial membrane,” stated Prof. Misgeld.

The researchers have applied the technique to two experimental models, and have arrived at some unexpected insights. On the one hand, they have been able for the first time to study redox signal induction in response to neural damage—in this instance, spinal cord injury—in the mammalian nervous system. The observations revealed that severance of an axon results in a wave of oxidation of the mitochondria, which begins at the site of damage and is propagated along the fiber. Furthermore, a flood of calcium at the site of axonal resection was shown to be needed for the subsequent functional damage to mitochondria.

Quite possibly the most unexpected outcome of the new study was that the study’s first author, graduate student Michael Breckwoldt, was able to image for the first time, spontaneous contractions of mitochondria that are accompanied by a rapid shift in the redox state of the organelle.

Prof. Misgeld concluded, “This appears to be a fail-safe system that is activated in response to stress and temporarily attenuates mitochondrial activity. Under pathological conditions, the contractions are more prolonged and may become irreversible, and this can ultimately result in irreparable damage to the nerve process.”

Related Links:

Technische Universität München
Ludwig-Maximilians-Universität München


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88 (41.961669921875): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294752311 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (35.04753112793): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (64.849853515625): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (34.809112548828): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (87.02278137207): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
105 (114.91775512695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
106 (79.154968261719): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294752311 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (76.055526733398): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294752311 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (110.86463928223): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
109 (106.8115234375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
110 (78.916549682617): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294752311 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (655.17425537109): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294752311 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (647.06802368164): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (352.85949707031): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (94.890594482422): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
115 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
116 (78.916549682617): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
117 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
118 (75.101852416992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
119 (102.04315185547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
120 (79.154968261719): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
121 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
122 (344.99168395996): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 62821.14982605): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (684.02290344238): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294752311 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294752311 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 18641.948699951): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (81.062316894531): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (42.915344238281): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (43.869018554688): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (63.896179199219): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (52.928924560547): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (540.97175598145): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (57.93571472168): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (65.088272094727): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (87.976455688477): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (576.97296142578): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (497.81799316406): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (52.928924560547): SELECT name FROM jos_deeppockets WHERE id=215
138 (35.04753112793): SELECT name FROM jos_deeppockets WHERE id=215
139 (739.81285095215): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (649.92904663086): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (97.990036010742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
142 (72.956085205078): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
143 (!!!!! 9891.0331726074): TRUNCATE TABLE jos_trademed_module
144 (128.03077697754): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294752311 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (293.01643371582): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294752311 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (594.13909912109): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (92.029571533203): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
149 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
150 (!!!!! 1667.0227050781): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (91.075897216797): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
152 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
153 (49.114227294922): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294752311 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294752311 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (41.961669921875): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=215 or channel_id is null)
155 (37.908554077148): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=215 or channel_id is null)
156 (45.061111450195): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (159.02519226074): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
158 (101.08947753906): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294752311 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294752311 AND published='1' LIMIT 1
159 (46.014785766602): select jos_twitters.link from jos_twitters where cat=10
160 (61.03515625): select jos_facebook.link from jos_facebook where cat=10
161 (35.04753112793): select jos_google_plus.link from jos_google_plus where cat=10
162 (85.115432739258): select jos_linkedin.link from jos_linkedin where cat=10
163 (293.01643371582): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14202,14203)
164 (!!!!! 1197.8149414062): insert into jos_banners_delta values (14202,'2025-06-23 11:23:04','216.73.216.120','view'),(14203,'2025-06-23 11:23:04','216.73.216.120','view')