Adenoviral-Mediated Modulation ofSim1Expression in the Paraventricular Nucleus Affects Food Intake

• DOI: 10.1523/jneurosci.0672-06.2006
• Publication Date: 2006-06-28T17:16:54Z
• Authors: Chun Yang; David Gagnon; Pascal Vachon; André Tremblay; Emile Levy; Bernard Massie; Jacques L. Michaud
• Keywords: Male; 0301 basic medicine; Time Factors; Cells; Mice,Inbred Strains; Genetic Vectors; Mice, Inbred Strains; Adenoviridae; Eating; Mice; 03 medical and health sciences; Basic Helix-Loop-Helix Transcription Factors; Animals; genetics; bio Basic Helix-Loop-Helix Transcription Factors; 2. Zero hunger; Protein; Gene Transfer Techniques; Brain; Proteins; 3. Good health; Repressor Proteins; physiology; Rna; RNA Interference; metabolism; biotechnology; Transcription Factors; Paraventricular Hypothalamic Nucleus

Haploinsufficency of Sim1, which codes for a basic helix-loop-helix-PAS (PER-ARNT-SIM) transcription factor, causes hyperphagia in mice and humans, without decrease energy expenditure. Sim1 is expressed several areas the brain, including developing postnatal paraventricular nucleus (PVN), region hypothalamus that controls food intake. We have previously found number PVN cells decreased Sim1+/- mice, suggesting their caused by developmental mechanism. However, possibility functions to control intake cannot be ruled out. To explore this hypothesis, we used adenoviral vectors modulate expression wild-type mice. Unilateral stereotaxic injection into an vector producing short hairpin RNA directed against resulted significant increase intake, peaked 22% 6 d after procedure, compared with virus. In contrast, adenovirus expresses induced was maximal on seventh day reaching 20%. The impact bilateral injections these not greater than unilateral injections. Together, results strongly suggest along physiological pathway