Journal article
Simultaneous Silencing of Npy and Dbh Expression in Hindbrain A1/C1 Catecholamine Cells Suppresses Glucoprivic Feeding
The Journal of neuroscience, Vol.29(1), pp.280-287
01/07/2009
Handle:
https://hdl.handle.net/2376/108285
PMCID: PMC2711634
PMID: 19129404
Abstract
Previous data have strongly implicated hindbrain catecholamine/neuropeptide Y (NPY) coexpressing neurons as key mediators of the glucoprivic feeding response. Catecholamine/NPY cell bodies are concentrated in the A1 and caudal C1 cell cluster (A1/C1) in the ventrolateral medulla, a region highly sensitive to glucoprivic challenge. To further investigate the importance of this catecholamine subpopulation in glucoregulation, we used small interfering RNA (siRNA) technology to produce a targeted gene knockdown of NPY and dopamine-β-hydroxylase (DBH), a catecholamine biosynthetic enzyme. Unilateral injection of NPY siRNA and DBH siRNA (0.02 nmol each) both significantly inhibited expression of the targeted genes up to 2 d, as revealed by real-time PCR, and reduced protein expression up to 8 d, as revealed by immunohistochemistry, compared with the control nontargeting siRNA (ntRNA) side. Subsequently, targeted siRNA or control ntRNA was injected bilaterally into A1/C1 and responses to 2-deoxy-
d
-glucose (2DG; 200 mg/kg)-induced glucoprivation were tested 3–7 d later. Silencing of either
Npy
or
Dbh
alone did not reduce glucoprivic feeding or hyperglycemic responses, compared with responses of ntRNA-injected controls. In contrast, simultaneous silencing of both
Npy
and
Dbh
reduced 2DG-induced feeding by 61%. Neither the hyperglycemic response to 2DG nor feeding elicited by mercaptoacetate (68 mg/kg)-induced blockade of fatty acid oxidation (“lipoprivic feeding”) was reduced by simultaneous silencing of these two genes. These results suggest that catecholamines and NPY act conjointly to control glucoprivic feeding and that the crucial NPY/catecholamine coexpressing neurons are concentrated in the A1/C1 cell group.
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Details
- Title
- Simultaneous Silencing of Npy and Dbh Expression in Hindbrain A1/C1 Catecholamine Cells Suppresses Glucoprivic Feeding
- Creators
- Ai-Jun Li - Programs in Neuroscience, Washington State University, Pullman, Washington 99164-6520Qing Wang - Programs in Neuroscience, Washington State University, Pullman, Washington 99164-6520Thu T Dinh - Programs in Neuroscience, Washington State University, Pullman, Washington 99164-6520Sue Ritter - Programs in Neuroscience, Washington State University, Pullman, Washington 99164-6520
- Publication Details
- The Journal of neuroscience, Vol.29(1), pp.280-287
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Society for Neuroscience
- Identifiers
- 99900547240901842
- Language
- English
- Resource Type
- Journal article