The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Bin Jiang - One of the best experts on this subject based on the ideXlab platform.
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tau deficiency down regulated transcription factor Orthodenticle Homeobox 2 expression in the dopaminergic neurons in ventral tegmental area and caused no obvious motor deficits in mice
Neuroscience, 2018Co-Authors: Xiaolu Tang, Luyan Jiao, Meige Zheng, Ting Wu, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Pingyi Xu, Jinhai DuanAbstract:Abstract Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau +/+ , tau +/− , tau −/− mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle Homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau +/+ mice, there were 54.1% lower ( p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau +/− mice and 43.6% lower ( p = 0.0249) OTX2 protein in VTA DA neurons of tau −/− mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson’s disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP.
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tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor Orthodenticle Homeobox 2 expression
The FASEB Journal, 2017Co-Authors: Meige Zheng, Xiaolu Tang, Luyan Jiao, Guofeng Zhang, Yonglin Li, Xianhong Xiang, Xingjian Li, Bin JiangAbstract:Homozygous tau knockout (Mapt−/−) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau i...
Alain Prochiantz - One of the best experts on this subject based on the ideXlab platform.
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Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes
Human Molecular Genetics, 2013Co-Authors: Clémence Bernard, Antonio Simeone, Manuel Simonutti, Raoul Torero Ibad, Serge Picaud, Dario Acampora, Ariel A. Di Nardo, Alain ProchiantzAbstract:: In the human, mutations of OTX2 (Orthodenticle Homeobox 2 transcription factor) translate into eye malformations of variable expressivity (even between the two eyes of the same individual) and incomplete penetrance, suggesting the existence of subtle thresholds in OTX2 activity. We have addressed this issue by analyzing retinal structure and function in six mutant mice with graded Otx2 activity: Otx2(+/+), Otx2(+/AA), Otx2(+/GFP), Otx2(AA/AA), Otx2(AA/GFP) and Otx2(GFP/GFP). Null mice (Otx2(GFP/GFP)) fail to develop the head and are embryonic lethal, and compound heterozygous Otx2(AA/GFP) mice show a truncated head and die at birth. All other genotypes develop until adulthood. We analyzed eye structure and visual physiology in the genotypes that develop until adulthood and report that phenotype severity parallels Otx2 activity. Otx2(+/AA) are only mildly affected whereas Otx2(+/GFP) are more affected than Otx2(+/AA) but less than Otx2(AA/AA) mice. Otx2(AA/AA) mice later manifest the most severe defects, with variable expressivity. Electrophysiological and histological analyses of the mouse retina revealed progressive death of bipolar cells and cone photoreceptors that is both Otx2 activity- and age-dependent with the same ranking of phenotypic severity. This study demonstrates the importance of gene dosage in the development of age-dependent pathologies and underscores the fact that small gene dosage differences can cause significant pathological states.
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Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex.
The Journal of Neuroscience, 2012Co-Authors: Marine Beurdeley, Clémence Bernard, Ariel A. Di Nardo, Julien Spatazza, Sayaka Sugiyama, Takao Hensch, Alain ProchiantzAbstract:Specific transfer of (Orthodenticle Homeobox 2) Otx2 homeoprotein into GABAergic interneurons expressing parvalbumin (PV) is necessary and sufficient to open, then close, a critical period (CP) of plasticity in the developing mouse visual cortex. The accumulation of endogenous Otx2 in PV cells suggests the presence of specific Otx2 binding sites. Here, we find that perineuronal nets (PNNs) on the surfaces of PV cells permit the specific, constitutive capture of Otx2. We identify a 15 aa domain containing an arginine-lysine doublet (RK peptide) within Otx2, bearing prototypic traits of a glycosaminoglycan (GAG) binding sequence that mediates Otx2 binding to PNNs, and specifically to chondroitin sulfate D and E, with high affinity. Accordingly, PNN hydrolysis by chondroitinase ABC reduces the amount of endogenous Otx2 in PV cells. Direct infusion of RK peptide similarly disrupts endogenous Otx2 localization to PV cells, reduces PV and PNN expression, and reopens plasticity in adult mice. The closure of one eye during this transient window reduces cortical acuity and is specific to the RK motif, as an Alanine-Alanine variant or a scrambled peptide fails to reactivate plasticity. Conversely, this transient reopening of plasticity in the adult restores binocular vision in amblyopic mice. Thus, one function of PNNs is to facilitate the persistent internalization of Otx2 by PV cells to maintain CP closure. The pharmacological use of the Otx2 GAG binding domain offers a novel, potent therapeutic tool with which to restore cortical plasticity in the mature brain.
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Development/Plasticity/Repair Otx2 Binding to Perineuronal Nets Persistently Regulates Plasticity in the Mature Visual Cortex
Journal of Neuroscience, 2012Co-Authors: Marine Beurdeley, Clémence Bernard, Julien Spatazza, Henry Lee, Sayaka Sugiyama, Ariel Di Nardo, Takao Hensch, Alain ProchiantzAbstract:Specific transfer of (Orthodenticle Homeobox 2) Otx2 homeoprotein into GABAergic interneurons expressing parvalbumin (PV) is necessary and sufficient to open, then close, a critical period (CP) of plasticity in the developing mouse visual cortex. The accumulation of endogenous Otx2 in PV cells suggests the presence of specific Otx2 binding sites. Here, we find that perineuronal nets (PNNs) on the surfaces of PV cells permit the specific, constitutive capture of Otx2. We identify a 15 aa domain containing an arginine-lysine doublet (RK peptide) within Otx2, bearing prototypic traits of a glycosaminoglycan (GAG) binding sequence that mediates Otx2 binding to PNNs, and specifically to chondroitin sulfate D and E, with high affinity. Accordingly, PNN hydrolysis by chondroitinase ABC reduces the amount of endogenous Otx2 in PV cells. Direct infusion of RK peptide similarly disrupts endogenous Otx2 localization to PV cells, reduces PV and PNN expression, and reopens plasticity in adult mice. The closure of one eye during this transient window reduces cortical acuity and is specific to the RK motif, as an Alanine-Alanine variant or a scrambled peptide fails to reactivate plasticity. Conversely, this transient reopening of plasticity in the adult restores binocular vision in amblyopic mice. Thus, one function of PNNs is to facilitate the persistent internalization of Otx2 by PV cells to maintain CP closure. The pharmacological use of the Otx2 GAG binding domain offers a novel, potent therapeutic tool with which to restore cortical plasticity in the mature brain.
Meige Zheng - One of the best experts on this subject based on the ideXlab platform.
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tau deficiency down regulated transcription factor Orthodenticle Homeobox 2 expression in the dopaminergic neurons in ventral tegmental area and caused no obvious motor deficits in mice
Neuroscience, 2018Co-Authors: Xiaolu Tang, Luyan Jiao, Meige Zheng, Ting Wu, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Pingyi Xu, Jinhai DuanAbstract:Abstract Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau +/+ , tau +/− , tau −/− mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle Homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau +/+ mice, there were 54.1% lower ( p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau +/− mice and 43.6% lower ( p = 0.0249) OTX2 protein in VTA DA neurons of tau −/− mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson’s disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP.
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tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor Orthodenticle Homeobox 2 expression
The FASEB Journal, 2017Co-Authors: Meige Zheng, Xiaolu Tang, Luyan Jiao, Guofeng Zhang, Yonglin Li, Xianhong Xiang, Xingjian Li, Bin JiangAbstract:Homozygous tau knockout (Mapt−/−) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau i...
Xiaolu Tang - One of the best experts on this subject based on the ideXlab platform.
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tau deficiency down regulated transcription factor Orthodenticle Homeobox 2 expression in the dopaminergic neurons in ventral tegmental area and caused no obvious motor deficits in mice
Neuroscience, 2018Co-Authors: Xiaolu Tang, Luyan Jiao, Meige Zheng, Ting Wu, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Pingyi Xu, Jinhai DuanAbstract:Abstract Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau +/+ , tau +/− , tau −/− mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle Homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau +/+ mice, there were 54.1% lower ( p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau +/− mice and 43.6% lower ( p = 0.0249) OTX2 protein in VTA DA neurons of tau −/− mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson’s disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP.
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tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor Orthodenticle Homeobox 2 expression
The FASEB Journal, 2017Co-Authors: Meige Zheng, Xiaolu Tang, Luyan Jiao, Guofeng Zhang, Yonglin Li, Xianhong Xiang, Xingjian Li, Bin JiangAbstract:Homozygous tau knockout (Mapt−/−) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau i...
Guofeng Zhang - One of the best experts on this subject based on the ideXlab platform.
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tau deficiency down regulated transcription factor Orthodenticle Homeobox 2 expression in the dopaminergic neurons in ventral tegmental area and caused no obvious motor deficits in mice
Neuroscience, 2018Co-Authors: Xiaolu Tang, Luyan Jiao, Meige Zheng, Ting Wu, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Pingyi Xu, Jinhai DuanAbstract:Abstract Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau +/+ , tau +/− , tau −/− mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle Homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau +/+ mice, there were 54.1% lower ( p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau +/− mice and 43.6% lower ( p = 0.0249) OTX2 protein in VTA DA neurons of tau −/− mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson’s disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP.
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tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor Orthodenticle Homeobox 2 expression
The FASEB Journal, 2017Co-Authors: Meige Zheng, Xiaolu Tang, Luyan Jiao, Guofeng Zhang, Yonglin Li, Xianhong Xiang, Xingjian Li, Bin JiangAbstract:Homozygous tau knockout (Mapt−/−) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau i...