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  • 1
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    Online Resource
    Tau-Induced Defects in Synaptic Plasticity, Learning, and Memory Are Reversible in Transgenic Mice after Switching Off the Toxic Tau Mutant
    Society for Neuroscience ; 2011
    In:  The Journal of Neuroscience Vol. 31, No. 7 ( 2011-02-16), p. 2511-2525
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 31, No. 7 ( 2011-02-16), p. 2511-2525
    Abstract: This report describes the behavioral and electrophysiological analysis of regulatable transgenic mice expressing mutant repeat domains of human Tau (Tau RD ). Mice were generated to express Tau RD in two forms, differing in their propensity for β-structure and thus in their tendency for aggregation (“pro-aggregant” or “anti-aggregant”) (Mocanu et al., 2008). Only pro-aggregant mice show pronounced changes typical for Tau pathology in Alzheimer's disease (aggregation, missorting, hyperphosphorylation, synaptic and neuronal loss), indicating that the β-propensity and hence the ability to aggregate is a key factor in the disease. We now tested the mice with regard to neuromotor parameters, behavior, learning and memory, and synaptic plasticity and correlated this with histological and biochemical parameters in different stages of switching Tau RD on or off. The mice are normal in neuromotor tests. However, pro-aggregant Tau RD mice are strongly impaired in memory and show pronounced loss of long-term potentiation (LTP), suggesting that Tau aggregation specifically perturbs these brain functions. Remarkably, when the expression of human pro-aggregant Tau RD is switched on for ∼10 months and off for ∼4 months, memory and LTP recover, whereas aggregates decrease moderately and change their composition from mixed human plus mouse Tau to mouse Tau only. Neuronal loss persists, but synapses are partially rescued. This argues that continuous presence of amyloidogenic pro-aggregant Tau RD constitutes the main toxic insult for memory and LTP, rather than the aggregates as such.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.5245-10.2011
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2011
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  • 2
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    The Potential for β-Structure in the Repeat Domain of Tau Protein Determines Aggregation, Synaptic Decay, Neuronal Loss, and Coassembly with Endogenous Tau in Inducible Mouse Models of Tauopathy
    Society for Neuroscience ; 2008
    In:  The Journal of Neuroscience Vol. 28, No. 3 ( 2008-01-16), p. 737-748
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 3 ( 2008-01-16), p. 737-748
    Abstract: We describe two new transgenic mouse lines for studying pathological changes of Tau protein related to Alzheimer's disease. They are based on the regulatable expression of the four-repeat domain of human Tau carrying the FTDP17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation ΔK280 (Tau RD /ΔK280), or the ΔK280 plus two proline mutations in the hexapeptide motifs (Tau RD /ΔK280/I277P/I308P). The ΔK280 mutation accelerates aggregation (“proaggregation mutant”), whereas the proline mutations inhibit Tau aggregation in vitro and in cell models (“antiaggregation mutant”). The inducible transgene expression was driven by the forebrain-specific CaMKIIα (calcium/calmodulin-dependent protein kinase IIα) promoter. The proaggregation mutant leads to Tau aggregates and tangles as early as 2–3 months after gene expression, even at low expression (70% of endogenous mouse Tau). The antiaggregation mutant does not aggregate even after 22 months of gene expression. Both mutants show missorting of Tau in the somatodendritic compartment and hyperphosphorylation in the repeat domain [KXGS motifs, targets of the kinase MARK (microtubule affinity regulating kinase)]. This indicates that these changes are related to Tau expression rather than aggregation. The proaggregation mutant causes astrogliosis, loss of synapses and neurons from 5 months of gene expression onward, arguing that Tau toxicity is related to aggregation. Remarkably, the human proaggregation mutant Tau RD coaggregates with mouse Tau, coupled with missorting and hyperphosphorylation at multiple sites. When expression of proaggregation Tau RD is switched off, soluble and aggregated exogenous Tau RD disappears within 1.5 months. However, tangles of mouse Tau, hyperphosphorylation, and missorting remain, suggesting an extended lifetime of aggregated wild-type Tau once a pathological conformation and aggregation is induced by a proaggregation Tau species.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2824-07.2008
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2008
    detail.hit.zdb_id: 1475274-8
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  • 3
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    The β-Propensity of Tau Determines Aggregation and Synaptic Loss in Inducible Mouse Models of Tauopathy
    Elsevier BV ; 2007
    In:  Journal of Biological Chemistry Vol. 282, No. 43 ( 2007-10), p. 31755-31765
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 282, No. 43 ( 2007-10), p. 31755-31765
    Type of Medium: Online Resource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.M705282200
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2007
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
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  • 4
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    Proteomic and biochemical responses to different concentrations of CO2 suggest the existence of multiple carbon metabolism strategies in Phaeodactylum tricornutum
    Springer Science and Business Media LLC ; 2021
    In:  Biotechnology for Biofuels Vol. 14, No. 1 ( 2021-12-14)
    Details
    In: Biotechnology for Biofuels, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2021-12-14)
    Abstract: Diatoms are well known for high photosynthetic efficiency and rapid growth rate, which are not only important oceanic primary producer, but also ideal feedstock for microalgae industrialization. Their high success is mainly due to the rapid response of photosynthesis to inorganic carbon fluctuations. Thus, an in-depth understanding of the photosynthetic carbon fixation mechanism of diatoms will be of great help to microalgae-based applications. This work directed toward the analysis of whether C4 photosynthetic pathway functions in the model marine diatom Phaeodactylum tricornutum , which possesses biophysical CO 2 -concentrating mechanism (CCM) as well as metabolic enzymes potentially involved in C4 photosynthetic pathway. Results For P. tricornutum , differential proteome, enzyme activities and transcript abundance of carbon metabolism-related genes especially biophysical and biochemical CCM-related genes in response to different concentrations of CO 2 were tracked in this study. The upregulated protein abundance of a carbonic anhydrases and a bicarbonate transporter suggested biophysical CCM activated under low CO 2 (LC). The upregulation of a number of key C4-related enzymes in enzymatic activity, transcript and protein abundance under LC indicated the induction of a mitochondria-mediated CCM in P. tricornutum . Moreover, protein abundance of a number of glycolysis, tricarboxylic acid cycle, photorespiration and ornithine–urea cycle related proteins upregulated under LC, while numbers of proteins involved in the Calvin cycle and pentose phosphate pathway were downregulated. Under high CO 2 (HC), protein abundance of most central carbon metabolism and photosynthesis-related proteins were upregulated. Conclusions The proteomic and biochemical responses to different concentrations of CO 2 suggested multiple carbon metabolism strategies exist in P. tricornutum . Namely, LC might induce a mitochondrial-mediated C4-like CCM and the improvement of glycolysis, tricarboxylic acid cycle, photorespiration and ornithine–urea cycle activity contribute to the energy supply and carbon and nitrogen recapture in P. tricornutum to cope with the CO 2 limitation, while P. tricornutum responds to the HC environment by improving photosynthesis and central carbon metabolism activity. These findings can not only provide evidences for revealing the global picture of biophysical and biochemical CCM in P. tricornutum , but also provide target genes for further microalgal strain modification to improve carbon fixation and biomass yield in algal-based industry.
    Type of Medium: Online Resource
    ISSN: 1754-6834
    URL: Article
    DOI: 10.1186/s13068-021-02088-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 3107320-7
    detail.hit.zdb_id: 2421351-2
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  • 5
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    Hippocampal Synapses Depend on Hippocampal Estrogen Synthesis
    Society for Neuroscience ; 2004
    In:  The Journal of Neuroscience Vol. 24, No. 26 ( 2004-06-30), p. 5913-5921
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 24, No. 26 ( 2004-06-30), p. 5913-5921
    Abstract: Estrogens have been described to induce synaptogenesis in principal neurons of the hippocampus and have been shown to be synthesized and released by exactly these neurons. Here, we have focused on the significance of local estrogen synthesis on spine synapse formation and the synthesis of synaptic proteins. To this end, we reduced hippocampal estrogen synthesis in vitro with letrozole, a reversible nonsteroidal aromatase inhibitor. In hippocampal slice cultures, letrozole treatment resulted in a dose-dependent decrease of 17β-estradiol as quantified by RIA. This was accompanied by a significant decrease in the density of spine synapses and in the number of presynaptic boutons. Quantitative immunohistochemistry revealed a downregulation of spinophilin, a marker of dendritic spines, and synaptophysin, a protein of presynaptic vesicles, in response to letrozole. Surprisingly, no increase in the density of spines, boutons, and synapses and in spinophilin expression was seen after application of estradiol to the medium of cultures that had not been treated with letrozole. However, synaptophysin expression was upregulated under these conditions. Our results point to an essential role of endogenous hippocampal estrogen synthesis in the maintenance of hippocampal spine synapses.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.5186-03.2004
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2004
    detail.hit.zdb_id: 1475274-8
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  • 6
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    Sex-Dependent Regulation of Aromatase-Mediated Synaptic Plasticity in the Basolateral Amygdala
    Society for Neuroscience ; 2017
    In:  The Journal of Neuroscience Vol. 37, No. 6 ( 2017-02-08), p. 1532-1545
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 37, No. 6 ( 2017-02-08), p. 1532-1545
    Abstract: The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17β-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM inhibitor letrozole reduced spine synapse density in the BL of adult female mice but not in the BL of male mice. Similarly, in organotypic corticoamygdalar slice cultures from immature rats, treatment with letrozole significantly reduced spine synapses in the BL only in cultures derived from females. In addition, letrozole sex-specifically altered synaptic properties in the BL: in acute slices from juvenile (prepubertal) female rats, wash-in of letrozole virtually abolished long-term potentiation (LTP), whereas it did not prevent the generation of LTP in the slices from males. Together, these data indicate that neuron-derived E2 modulates synaptic plasticity in rodent BLA sex-dependently. As protein expression levels of AROM, estrogen and androgen receptors did not differ between males and females and were not sex-specifically altered by letrozole, the findings suggest sex-specific mechanisms of E2 signaling. SIGNIFICANCE STATEMENT The basolateral amygdala (BLA) is a key structure of the fear circuit. This research reveals a sexually dimorphic regulation of synaptic plasticity in the BLA involving neuronal aromatase, which produces the neurosteroid 17β-estradiol (E2). As male and female neurons in rodent BLA responded differently to aromatase inhibition both in vivo and in vitro , our findings suggest that E2 signaling in BLA neurons is regulated sex-dependently, presumably via mechanisms that have been established during sexual determination. These findings could be relevant for the understanding of sex differences in mood disorders and of the side effects of cytochrome P450 aromatase inhibitors, which are frequently used for breast cancer therapy.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.1532-16.2016
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2017
    detail.hit.zdb_id: 1475274-8
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  • 7
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    Estrogen-regulated synaptogenesis in the hippocampus: Sexual dimorphism in vivo but not in vitro
    Elsevier BV ; 2012
    In:  The Journal of Steroid Biochemistry and Molecular Biology Vol. 131, No. 1-2 ( 2012-8), p. 24-29
    Details
    In: The Journal of Steroid Biochemistry and Molecular Biology, Elsevier BV, Vol. 131, No. 1-2 ( 2012-8), p. 24-29
    Type of Medium: Online Resource
    ISSN: 0960-0760
    URL: Article
    DOI: 10.1016/j.jsbmb.2011.11.010
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2012
    detail.hit.zdb_id: 1482780-3
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  • 8
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    Chlorophyll fluorescence as a light signal enhances iron uptake by the marine diatom Phaeodactylum tricornutum under high-cell density conditions
    Springer Science and Business Media LLC ; 2021
    In:  BMC Biology Vol. 19, No. 1 ( 2021-12)
    Details
    In: BMC Biology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: Diatoms usually dominate phytoplankton blooms in open oceans, exhibiting extremely high population densities. Although the iron uptake rate of diatoms largely determines the magnitude and longevity of diatom blooms, the underlying mechanisms regulating iron uptake remain unclear. Results The transcription of two iron uptake proteins, ISIP2a and ISIP1, in the marine diatom Phaeodactylum tricornutum was enhanced with increasing cell density, whereas the cellular iron content showed the opposite trend. When compared with the wild-type strain, knockdown of ISIP2a resulted in 43% decrease in cellular iron content, implying the involvement of ISIP2a in iron uptake under high-cell density conditions. Incubation of the diatom cells with sonicated cell lysate conditioned by different cell densities did not affect ISIP2a and ISIP1 expression, ruling out regulation via chemical cues. In contrast, ISIP2a and ISIP1 transcription were strongly induced by red light. Besides, chlorophyll fluorescence excited from the blue light was also positively correlated with population density. Subsequently, a “sandwich” illumination incubator was designed to filter out stray light and ensure that the inner layer cells only receive the emitted chlorophyll fluorescence from outer layers, and the results showed that the increase in outer cell density significantly elevated ISIP2a and ISIP1 transcription in inner layer cells. In situ evidence from Tara oceans also showed positively correlated between diatom ISIP transcripts and chlorophyll content. Conclusions This study shows that chlorophyll fluorescence derived from neighboring cells is able to upregulate ISIP2a and ISIP1 expression to facilitate iron assimilation under high-cell density. These results provide novel insights into biotic signal sensing in phytoplankton, which can help to elucidate the underlying mechanisms of marine diatom blooms.
    Type of Medium: Online Resource
    ISSN: 1741-7007
    URL: Article
    DOI: 10.1186/s12915-021-01177-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2133020-7
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  • 9
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    Endocrine regulation of estrogen synthesis in the hippocampus?
    Elsevier BV ; 2013
    In:  Progress in Histochemistry and Cytochemistry Vol. 48, No. 2 ( 2013-8), p. 49-64
    Details
    In: Progress in Histochemistry and Cytochemistry, Elsevier BV, Vol. 48, No. 2 ( 2013-8), p. 49-64
    Type of Medium: Online Resource
    ISSN: 0079-6336
    URL: Article
    DOI: 10.1016/j.proghi.2013.07.002
    RVK:
    WE 6000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 123072-4
    detail.hit.zdb_id: 2164754-9
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  • 10
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    Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis
    Rockefeller University Press ; 2008
    In:  The Journal of Cell Biology Vol. 180, No. 2 ( 2008-01-28), p. 417-426
    Details
    In: The Journal of Cell Biology, Rockefeller University Press, Vol. 180, No. 2 ( 2008-01-28), p. 417-426
    Abstract: Spine density in the hippocampus changes during the estrus cycle and is dependent on the activity of local aromatase, the final enzyme in estrogen synthesis. In view of the abundant gonadotropin-releasing hormone receptor (GnRH-R) messenger RNA expression in the hippocampus and the direct effect of GnRH on estradiol (E2) synthesis in gonadal cells, we asked whether GnRH serves as a regulator of hippocampal E2 synthesis. In hippocampal cultures, E2 synthesis, spine synapse density, and immunoreactivity of spinophilin, a reliable spine marker, are consistently up-regulated in a dose-dependent manner at low doses of GnRH but decrease at higher doses. GnRH is ineffective in the presence of GnRH antagonists or aromatase inhibitors. Conversely, GnRH-R expression increases after inhibition of hippocampal aromatase. As we found estrus cyclicity of spine density in the hippocampus but not in the neocortex and GnRH-R expression to be fivefold higher in the hippocampus compared with the neocortex, our data strongly suggest that estrus cycle–dependent synaptogenesis in the female hippocampus results from cyclic release of GnRH.
    Type of Medium: Online Resource
    ISSN: 1540-8140 , 0021-9525
    URL: Article
    DOI: 10.1083/jcb.200707043
    RVK:
    WA 15000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2008
    detail.hit.zdb_id: 1421310-2
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