Organ specific optical imaging of mitochondrial redox state in a rodent model of hereditary hemorrhagic telangiectasia‐1

Maleki, Sepideh; Park, Sunyoung; Sorenson, Christine M.; Ranji, Mahsa

doi:10.1002/jbio.201300033

Cited by 7 publications

(7 citation statements)

References 72 publications

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“…These findings suggest that PCB exposure during development induces changes in the functioning of the AC. In addition, this effect occurred without alterations in ratios of FAD+/NADH, which are used as measures of oxidative stress and mitochondrial function within and outside of the central nervous system (Gerich et al, 2009; Stebbings et al, 2016; Ghanian et al, 2014). Importantly, these results illustrate that PCB exposure during the developmental period can result in long-term changes in the physiology of the AC.…”

Section: Discussionmentioning

confidence: 99%

Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABA A antagonism

et al. 2016

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Developmental exposure of rats to polychlorinated biphenyls (PCBs) causes impairments in hearing and in the functioning of peripheral and central auditory structures. Additionally, recent work from our laboratory has demonstrated an increase in audiogenic seizures. The current study aimed to further characterize the effects of PCBs on auditory brain structures by investigating whether developmental exposure altered the magnitude of activation in the auditory cortex (AC) in response to electrical stimulation of thalamocortical afferents. Long-Evans female rats were fed cookies containing either 0 or 6 mg/kg of an environmental PCB mixture daily from 4 weeks prior to breeding until postnatal day 21. Brain slices containing projections from the thalamus to the AC were collected from adult female offspring and were bathed in artificial cerebrospinal fluid (aCSF) alone, aCSF containing a gamma-aminobutyric acid (GABA) receptor antagonist (200 nM SR95531), and aCSF containing an and N-methyl-D-aspartate (NMDA) receptor antagonist (50μM AP5). During each of these drug conditions, electrical stimulations ranging from 25-600 μA were delivered to the thalamocortical afferents. Activation of the AC was measured using flavoprotein autofluorescence imaging. Although there were no differences seen between treatment groups in the aCSF condition, there were significant increases in the ratio of aCSF/SR95531 activation in slices from PCB-exposed animals compared to control animals. This effect was seen in both the upper and lower layers of the AC. No differences in activation were noted between treatment groups when slices were exposed to AP5. These data suggest that developmental PCB exposure leads to increased sensitivity to antagonism of GABAA receptors in the AC without a change in NMDA-mediated intrinsic excitability.

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Section: Discussionmentioning

confidence: 99%

Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABA A antagonism

et al. 2016

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“…Higher signal acquisition leads to more precise measurement and a greater depth of the fluorescence signal. Lastly, rapid freezing of the tissue with liquid N 2 provides a snapshot of its metabolism at a specific moment in space and time [18] – [22] .…”

Section: Introductionmentioning

confidence: 99%

Optical Cryoimaging Reveals a Heterogeneous Distribution of Mitochondrial Redox State in ex vivo Guinea Pig Hearts and its Alteration during Ischemia and Reperfusion

Ranji

Motlagh

Salehpour

et al. 2016

IEEE J. Transl. Eng. Health Med.

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Oxidation of substrates to generate ATP in mitochondria is mediated by redox reactions of NADH and FADH2. Cardiac ischemia and reperfusion (IR) injury compromises mitochondrial oxidative phosphorylation. We hypothesize that IR alters the metabolic heterogeneity of mitochondrial redox state of the heart that is only evident in the 3-D optical cryoimaging of the perfused heart before, during, and after IR. The study involved four groups of hearts: time control (TC: heart perfusion without IR), global ischemia (Isch), global ischemia followed by reperfusion (IR) and TC with PCP (a mitochondrial uncoupler) perfusion. Mitochondrial NADH and FAD autofluorescence signals were recorded spectrofluorometrically online in guinea pig ex vivo-perfused hearts in the Langendorff mode. At the end of each specified protocol, hearts were rapidly removed and snap frozen in liquid N2 for later 3-D optical cryoimaging of the mitochondrial NADH, FAD, and NADH/FAD redox ratio (RR). The TC hearts revealed a heterogeneous spatial distribution of NADH, FAD, and RR. Ischemia and IR altered the spatial distribution and caused an overall increase and decrease in the RR by 55% and 64%, respectively. Uncoupling with PCP resulted in the lowest level of the RR (73% oxidation) compared with TC. The 3-D optical cryoimaging of the heart provides novel insights into the heterogeneous distribution of mitochondrial NADH, FAD, RR, and metabolism from the base to the apex during ischemia and IR. This 3-D information of the mitochondrial redox state in the normal and ischemic heart was not apparent in the dynamic spectrofluorometric data.

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“…The mitochondrial metabolic coenzymes (NADH and FADH2) are primary electron donors and acceptors in oxidative phosphorylation, respectively [37][38][39][40][41][42][43][44] . NADH and FAD (the oxidized form of FADH2) are autofluorescent and can be optically monitored without the addition of exogenous labels [37][38][39][40][41][42][43][44] . By imaging these two coenzymes, it is possible to probe the mitochondrial redox state of the retina at cryogenic temperature.…”

Section: Discussionmentioning

confidence: 99%

“…By imaging these two coenzymes, it is possible to probe the mitochondrial redox state of the retina at cryogenic temperature. The fluorescent signals of these two fluorophores have been used as an indicator of tissue metabolism in multiple animal injury models [38][39][40][41][42][43][44] . To the best of our knowledge, there has been no other study that has examined mitochondrial redox state expression in intact eye tissue before and after NIR-PBM.…”

Section: Discussionmentioning

confidence: 99%

Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa

Gopalakrishnan

Mehrvar

Maleki

et al. 2020

Sci Rep

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Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm2; 4.5 J/cm2) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.

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Organ specific optical imaging of mitochondrial redox state in a rodent model of hereditary hemorrhagic telangiectasia‐1

Cited by 7 publications

References 72 publications

Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABA A antagonism

Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABA A antagonism

Optical Cryoimaging Reveals a Heterogeneous Distribution of Mitochondrial Redox State in ex vivo Guinea Pig Hearts and its Alteration during Ischemia and Reperfusion

Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa

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