The Effects of Leptin Antagonist on Hypothalamic Neuropeptide Y Circuitry in Infantile Male Lambs.
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It is proposed that leptin signaling during infantile development is critical for structural organization of hypothalamic circuitry involved in the control of food intake and energy expenditure. The present study tested the hypothesis that disruption of leptin signaling alters the NPY circuitry in the hypothalamus of infantile lambs. Twelve neonatal Dorset X Finn male lambs were assigned randomly to one of three experimental groups (n = 4/group): 1) Early Antagonist (EA), 2) Late Antagonist (LA) and 3) Control (CN). Lambs in the EA group were injected i.v. with 0.23 mg/Kg0.75 of pegylated super ovine leptin antagonist (PEG-SOLA) twice daily from birth to postnatal Day 14. Concurrently, lambs in the LA and CN groups were injected with an equivalent volume of physiological saline. From postnatal Day 30 to 36, lambs in the LA group were injected i.v. with 0.46 mg/Kg0.75 of PEG-SOLA twice daily, while lambs in the CN and EA groups were injected with physiological saline. On postnatal Day 40, lambs were euthanized, and a block of tissue containing the hypothalamus was collected and processed for detection of NPY by immunocytochemistry. The distribution of NPY fibers in tissue sections was observed using bright-field microscopy and images representing various regions of the hypothalamus were captured using a 10X objective. The area covered by NPY-immunoreactive fibers was determined in regions of interest to represent the density of NPY fibers within each hypothalamic area analyzed. The mean density of NPY fibers did not differ significantly among the three treatment groups in any of the areas studied; however, the area covered by NPY fibers in the paraventricular nucleus tended to be greater in lambs treated with leptin antagonist early during the infantile period than in the control and late antagonist groups. Results of this study indicate that short-term disruption of leptin signaling during the infantile period does not clearly alter the density of NPY fibers in the hypothalamus of lambs. Additional studies should investigate whether other functional aspects of the NPY system (e.g., NPY synthesis and projections to target cells) are disrupted by leptin antagonist.
Bedenbaugh, Michelle (2012). The Effects of Leptin Antagonist on Hypothalamic Neuropeptide Y Circuitry in Infantile Male Lambs.. Honors and Undergraduate Research. Available electronically from