Neurons express hemoglobin α‐ and β‐chains in rat and human brains

Richter, Franziska; Meurers, Bernhard H.; Zhu, Chunni; Medvedeva, Vera; Chesselet, Marie‐Françoise

doi:10.1002/cne.22062

Cited by 192 publications

(176 citation statements)

References 44 publications

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“…GFAP expression rose dramatically in response to treatment with RPCs, suggesting higher glial activity (confirmed by immunohistochemistry, see Figure 4). Hba-a1 was downregulated after rotenone treatment as expected 22 and upregulated in RPC-treated samples. Hba-a1 is expressed in the apoptosis-like processes that take place as differentiating lens fibre cells lose their nuclei, without dying.…”

Section: Molecular Markerssupporting

confidence: 67%

“…Genes that were chosen on the basis of mitochondrial function (MTND1, 4, 6, Cox4i2, Cox6a2, NdufaF1), were glial markers (GFAP), GCL markers (Sncg, CHaT, Atoh7, Gad1, Gabbr, Isl1, Rbfox3, Syp, Th, Thy1), those that had apoptotic/cell cycle functions (Ccd1, Ki67, Bad, Bax, Bcl2) or were rotenone responsive and upregulated in glaucoma (Hba-a1, Hbb-b1 and 2). 22,23 Following the initial screening process, we included RPC-treated samples and rescreened rotenone responsive genes via qPCR. Nine genes showed differential expression in response to the treatment; MTND1 is also shown as it is mutated in LHON (see Figure 3a-j).…”

Section: Molecular Markersmentioning

confidence: 99%

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Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

et al. 2014

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Primary mitochondrial disorders occur at a prevalence of one in 10 000; B50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease. INTRODUCTIONPrimary mitochondrial disorders (those caused by mutations in the mitochondrial genome) occur at a prevalence of B1 in 10 000, with 1 in 200 individuals carrying at-risk mutations. 1 Approximately 50% demonstrate some form of ocular pathology. 2 Mitochondria provide energy in the form of ATP generated by oxidative phosphorylation; therefore, mitochondrial mutations primarily affect tissues with the greatest energy requirements, such as the retina, the inner ear, central and peripheral nervous systems and cardiac and skeletal muscle. 2,3 Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder, with a prevalence of B1 in 31 000-50 000 in northern Europe. The prevalence of at-risk carriers is much higher, estimated at 1 in 8 500 in the UK; furthermore, primary LHON mutations were found in 1 out of 350 neonatal umbilical cord samples. 1,4 LHON is maternally inherited, often results from homoplasmy of the causative mitochondrial mutation, and is incompletely penetrant; visual loss occurs in 50% of males and 10% of females. Symptoms result from retinal ganglion cell (RGC) pathology, which leads to RGC death via apoptosis, resulting in optic nerve degeneration and subsequent blindness. Nonocular symptoms of mitochondrial dysfunction may also be present. 1,4 Although many mutations implicated in LHON have been described, 90-95% of the cases result from one of the three common mutations in mitochondrial genes including MTND1, MTND4 and MTND6, which encode elements of ...

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Section: Molecular Markerssupporting

confidence: 67%

Section: Molecular Markersmentioning

confidence: 99%

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

et al. 2014

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“…The list of probesets was then filtered to remove any probesets that had been removed from our analysis during genuine signals rather than an artefact. In recent years there have been a growing number of reports of hemoglobin expression in a range of other tissues including neurons, 14 macrophages, 15 alveolar epithelial cells, 16 lens 17 and myelin. 18 This suggests that hemoglobin may play a more general role in oxygen balance within many cell types.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes selectively disallowed in the pancreatic islet

Pullen

Khan²,

Barton³

et al. 2010

Islets

157

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“…Although endogenous neuronal (non-erythrocyte) hemoglobin has been found in neurons of rodents and human brain, its function is still not fully clear (Richter et al 2009, He et al 2010. However, it has been shown that Hbb was kept as a separate entity in the analysis due to a unique robust response to GH (see 'Materials and methods').…”

Section: Effects Of Gh Administration With Respect To Plasticity Andmentioning

confidence: 99%

Different modes of GH administration influence gene expression in the male rat brain

Walser

Schiöler

Oscarsson

et al. 2014

Journal of Endocrinology

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The endogenous secretion pattern in males of GH is episodic in rats and in humans, whereas GH administration is usually even. Different types of GH administration have different effects on body mass, longitudinal bone growth, and liver metabolism in rodents, whereas possible effects on brain plasticity have not been investigated. In this study, GH was administered as a continuous infusion or as two daily injections in hypophysectomized male rats. Thirteen transcripts previously known to respond to GH in the hippocampus and parietal cortex (cortex) were assessed by RT-PCR. To investigate the effects of type of GH administration on several transcripts with different variations, and categories of transcripts (neuron-, glia-, and GH-related), a mixed model analysis was applied. Accordingly, GH injections increased overall transcript abundance more than GH infusions (21% in the hippocampus, P!0.001 and 10% in the cortex, PZ0.09). Specifically, GH infusions and injections robustly increased neuronal hemoglobin beta (Hbb) expression significantly (1.8-to 3.6-fold), and GH injections were more effective than GH infusions in increasing Hbb in the cortex (41%, PZ0.02), whereas a 23% difference in the hippocampus was not significant. Also cortical connexin 43 was higher in the group with GH injections than in those with GH infusions (26%, P!0.007). Also, there were differences between GH injections and infusions in GH-related transcripts of the cortex (23%, PZ0.04) and glia-related transcripts of the hippocampus (15%, PZ0.02). Thus, with the exception of Hbb there is a moderate difference in responsiveness to different modes of GH administration.

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Neurons express hemoglobin α‐ and β‐chains in rat and human brains

Cited by 192 publications

References 44 publications

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

Identification of genes selectively disallowed in the pancreatic islet

Different modes of GH administration influence gene expression in the male rat brain

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