Bugarith KH, Li A, Dinh TT, Ritter S (2004) Injection of the targeted-toxin, neuropeptide Y-saporin (NPY-SAP), into the basomedial hypothalamus (BMH) disrupts leptin and ghrelin signaling. Neuroscience 2004 Abstracts 893.17. Society for Neuroscience, San Diego, CA.
Summary: NPY-SAP, a conjugate of the peptide NPY and saporin, a ribosomal inactivating toxin, specifically lesions NPY receptor-expressing cells. We injected NPY-SAP into the BMH and examined the effects of various inhibitory (leptin, 5ug/5ul/day, icv; GLP-1, 5ug/5ul, icv, CCK, 4ug/kg, ip;) and stimulatory (ghrelin, 2ug/5ul, icv; NPY, 500ng/100nl, icv; 2-DG, 100, 200 and 400 mg/kg; MA, 68mg/kg, ip) peptide and metabolic signals that influence food intake. We also examined the effect of NPY-SAP on NPY, CART and AGRP mRNA expression in NPY/AGRP and POMC/CART neurons known to express the NPY receptor, and the effect of NPY and NPY Y1 receptor immunoreactivity in the arcuate (Arc) nucleus. We found that the anorectic effects of leptin and the orexigenic effects of ghrelin were abolished by NPY-SAP. The stimulation of feeding induced by NPY, 2-DG and MA, and the suppression of deprivation-induced feeding by GLP-1 and CCK were not attenuated by NPY-SAP injection. There was a profound but localized reduction of NPY Y1 receptor-, and NPY fiber and terminal immunoreactivity, and NPY, AGRP and CART mRNA expression in the Arc. NPY-SAP did not appear to be retrogradely transported in hindbrain NPY neurons with hypothalamic terminals. Leptin and ghrelin are thought to act primarily on Arc NPY/AGRP and POMC/CART neurons to mediate their ingestive effects, whereas the effects of 2-DG, MA, CCK and GLP-1 are thought to be mediated in part by mechanisms outside the Arc. Present results show that BMH injections of NPY-SAP selectively impair controls mediated by Arc neural circuitry without causing widespread disruption of other ingestive behaviors. Results also reveal important ingestive controls that do not require Arc NPY/AGRP and POMC/CART neurons.
Related Products: NPY-SAP (Cat. #IT-28)