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1.
PLoS Genet ; 9(12): e1004011, 2013.
Article in English | MEDLINE | ID: mdl-24385919

ABSTRACT

Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O2 and CO2. CO2 is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO2 changes. CO2 evokes distinct AFD Ca²âº responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO2 responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO2. Surprisingly, gradients of 0.01% CO2/second evoke very different Ca²âº responses from gradients of 0.04% CO2/second. Ambient O2 provides further contextual modulation of CO2 avoidance. At 21% O2 tonic signalling from the O2-sensing neuron URX inhibits CO2 avoidance. This inhibition can be graded according to O2 levels. In a natural wild isolate, a switch from 21% to 19% O2 is sufficient to convert CO2 from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O2 on CO2 avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO2-evoked Ca²âº responses. Ambient O2 and acclimation temperature act combinatorially to modulate CO2 responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans.


Subject(s)
Carbon Dioxide/metabolism , Neurons/metabolism , Oxygen/metabolism , Sensory Receptor Cells/metabolism , Synaptic Transmission/genetics , Animals , Animals, Genetically Modified , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/physiology , Calcium/metabolism , Mutation , Sensory Receptor Cells/physiology , Temperature
2.
Genes Cells ; 17(5): 365-86, 2012 May.
Article in English | MEDLINE | ID: mdl-22512337

ABSTRACT

Although a large proportion of molecules expressed in the nervous system are conserved from invertebrate to vertebrate, functional properties of such molecules are less characterized. Here, we show that highly conserved hydrolase AHO-3 acts as a novel regulator of starvation-induced thermotactic plasticity in Caenorhabditis elegans. As wild-type animals, aho-3 mutants migrated to the cultivation temperature on a linear thermal gradient after cultivation at a particular temperature with food. Whereas wild-type animals cultivated under food-deprived condition showed dispersed distribution on the gradient, aho-3 mutants exhibited tendency to migrate toward higher temperature. Such an abnormal behavior was completely rescued by the expression of human homologue of AHO-3, indicating that the molecular function of AHO-3 is highly conserved between nematode and human. The behavioral regulation by AHO-3 requires the N-terminal cysteine cluster, which ensures the proper subcellular localization of AHO-3 to sensory endings. Double-mutant analysis suggested that AHO-3 acts in the same pathway with ODR-3, a heterotrimeric G protein alpha subunit. Our results unveiled a novel neural protein in C. elegans, confirming its conserved role in behavioral regulation.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/physiology , Hydrolases/genetics , Amino Acid Sequence , Animals , Animals, Genetically Modified , Behavior, Animal/physiology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/metabolism , Food Deprivation , Humans , Hydrolases/metabolism , Locomotion/physiology , Molecular Sequence Data , Sequence Alignment , Temperature
3.
Biosci Biotechnol Biochem ; 75(12): 2394-7, 2011.
Article in English | MEDLINE | ID: mdl-22146724

ABSTRACT

We investigated the effects of vitamin C administration on vitamin C-specific transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter levels increased in the livers of the rats not administered vitamin C and decreased in the livers of those administered vitamin C at 100 mg/d, indicating that these transporter levels can be influenced by the amount of vitamin C administered.


Subject(s)
Ascorbic Acid/metabolism , Ascorbic Acid/pharmacology , Gene Expression Regulation/drug effects , Liver/drug effects , Liver/metabolism , Sodium-Coupled Vitamin C Transporters/genetics , Administration, Oral , Animals , Ascorbic Acid/administration & dosage , Hepatocytes/drug effects , Hepatocytes/metabolism , Liver/cytology , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats
4.
Neuron ; 69(6): 1099-113, 2011 Mar 24.
Article in English | MEDLINE | ID: mdl-21435556

ABSTRACT

Homeostatic control of body fluid CO(2) is essential in animals but is poorly understood. C. elegans relies on diffusion for gas exchange and avoids environments with elevated CO(2). We show that C. elegans temperature, O(2), and salt-sensing neurons are also CO(2) sensors mediating CO(2) avoidance. AFD thermosensors respond to increasing CO(2) by a fall and then rise in Ca(2+) and show a Ca(2+) spike when CO(2) decreases. BAG O(2) sensors and ASE salt sensors are both activated by CO(2) and remain tonically active while high CO(2) persists. CO(2)-evoked Ca(2+) responses in AFD and BAG neurons require cGMP-gated ion channels. Atypical soluble guanylate cyclases mediating O(2) responses also contribute to BAG CO(2) responses. AFD and BAG neurons together stimulate turning when CO(2) rises and inhibit turning when CO(2) falls. Our results show that C. elegans senses CO(2) using functionally diverse sensory neurons acting homeostatically to minimize exposure to elevated CO(2).


Subject(s)
Behavior, Animal/physiology , Carbon Dioxide , Homeostasis/physiology , Oxygen , Sensory Receptor Cells/physiology , Sodium Chloride , Animals , Caenorhabditis elegans , Calcium/metabolism , Ion Channel Gating/physiology , Motor Activity/physiology
5.
Brain Dev ; 32(3): 244-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19278800

ABSTRACT

We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.


Subject(s)
Cytokines/metabolism , Nerve Fibers, Myelinated/pathology , Tay-Sachs Disease/metabolism , Tay-Sachs Disease/pathology , Anti-Inflammatory Agents/therapeutic use , Child, Preschool , Dexamethasone/therapeutic use , Female , Glycerol/therapeutic use , Humans , Magnetic Resonance Imaging/methods , Tay-Sachs Disease/drug therapy
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