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  • 1
    Publication Date: 2016-03-24
    Description: Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP-TRPV1). Neuronal inhibition via the same stimuli is achieved by mutating the TRPV1 pore, rendering the channel chloride-permeable. These constructs were targeted to glucose-sensing neurons in the ventromedial hypothalamus in glucokinase-Cre mice, which express Cre in glucose-sensing neurons. Acute activation of glucose-sensing neurons in this region increases plasma glucose and glucagon, lowers insulin levels and stimulates feeding, while inhibition reduces blood glucose, raises insulin levels and suppresses feeding. These results suggest that pancreatic hormones function as an effector mechanism of central nervous system circuits controlling blood glucose and behaviour. The method we employ obviates the need for permanent implants and could potentially be applied to study other neural processes or used to regulate other, even dispersed, cell types.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stanley, Sarah A -- Kelly, Leah -- Latcha, Kaamashri N -- Schmidt, Sarah F -- Yu, Xiaofei -- Nectow, Alexander R -- Sauer, Jeremy -- Dyke, Jonathan P -- Dordick, Jonathan S -- Friedman, Jeffrey M -- GM067545/GM/NIGMS NIH HHS/ -- GM095654/GM/NIGMS NIH HHS/ -- MH105941/MH/NIMH NIH HHS/ -- U01 MH105941/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 31;531(7596):647-50. doi: 10.1038/nature17183. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA. ; Department of Chemical &Biological Engineering, Center for Biotechnology &Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA. ; Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA. ; Howard Hughes Medical Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/*metabolism ; Eating/*physiology ; Ferritins/genetics/metabolism ; Glucagon/blood ; Glucokinase/metabolism ; Homeostasis ; Hypoglycemia/metabolism ; Insulin/blood ; Integrases/metabolism ; *Magnetic Fields ; Mice ; Neural Inhibition ; Neurons/*physiology ; Pancreatic Hormones/metabolism ; *Radio Waves ; Recombinant Fusion Proteins/genetics/metabolism ; TRPV Cation Channels/genetics/metabolism ; Time Factors ; Ventromedial Hypothalamic Nucleus/*cytology/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-05-05
    Description: Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646550/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646550/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stanley, Sarah A -- Gagner, Jennifer E -- Damanpour, Shadi -- Yoshida, Mitsukuni -- Dordick, Jonathan S -- Friedman, Jeffrey M -- R01 GM095654/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 May 4;336(6081):604-8. doi: 10.1126/science.1216753.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics, Rockefeller University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22556257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bioengineering ; Blood Glucose/*analysis ; Calcium/*metabolism ; Embryonic Stem Cells/metabolism ; Epitopes ; *Ferric Compounds ; Ferritins/administration & dosage/genetics/metabolism ; HEK293 Cells ; Hot Temperature ; Humans ; Insulin/blood/genetics/*metabolism ; Male ; *Metal Nanoparticles ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental/blood/pathology ; PC12 Cells ; *Radio Waves ; Rats ; Recombinant Fusion Proteins/administration & dosage ; TRPV Cation Channels/genetics/immunology/*metabolism ; Transfection ; Transplantation, Heterologous
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillan Magazines Ltd.
    Nature 409 (2001), S. 258-268 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Biocatalytic processes can now be carried out in organic solvents as well as aqueous environments, so that apolar organic compounds as well as water-soluble compounds can be modified selectively and ...
    Type of Medium: Electronic Resource
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