Zhou D, Levin BE (2004) PVN anti-SERT-SAP injections reduce body weight gain, normal and glucoprivic feeding, and hypoglycemia- and stress-induced corticosterone responses. Neuroscience 2004 Abstracts 893.14. Society for Neuroscience, San Diego, CA.
Summary: Hindbrain serotonin (5HT) neurons are highly ramified with single neurons innervating several forebrain and hypothalamic areas such as the paraventricular nucleus (PVN). To assess their importance in the regulation of energy homeostasis and hypothalamo-pituitary-adrenal activation, anti-SERT-SAP (SS), an antibody to the 5HT re-uptake transporter (SERT) conjugated to a ribosomal toxin saporin (SAP), was injected bilaterally into the PVN of rats to selectively destroy hypothalamically-projecting 5HT neurons. Unconjugated SAP injections served as controls. SS injections significantly destroyed rostral dorsal (DRa) and medial raphe (MRa) 5HT neurons. Compared to SAP rats, SS rats had 13% lower food intake (SAP 71.2+3.2g vs. SS 61.7+2.8g, P=0.037) and 44% lower body weight gain (SAP 26.9+2.9g vs. SS 15.3+.31g, P=0.003) over 8d. Food intake over 24h (but not 3h) after insulin-induced hypoglycemia was 22% lower in SS (25.1±1.2g) than SAP rats (32.2±0.9g, P<0.01) and their blood glucose levels dropped more during 120min of hypoglycemia (AUC, -3945+77mg/dl) than SAP controls (-3675+108; P=0.01) suggesting a counterregulatory defect. This was supported by a 39% lower 30min corticosterone (Cort) response to hypoglycemia in SS (126±25µg/ml) vs. SAP controls (208±21 μg/ml, P<0.05). On the other hand, the glucagon response to hypoglycemia did not differ between SS (81.3±10.1pg/ml) and SAP-injected rats (65.8±7.6pg/ml; P=0.72). Finally, SS injections reduced the Cort response to 30min immobilization stress (SS 389±21 vs. SAP 460±25 µg/mg; P<0.05) by 15% without significantly affecting basal levels (SS 18.0±3.9 vs. SAP 10.1±2.2 µg/ml, P=0.09). Thus, DRa and MRa 5HT projections to the forebrain play a significant role in energy homeostasis, hypoglycemia-induced feeding and the Cort responses to both hypoglycemia and stress.
Related Products: Anti-SERT-SAP (Cat. #IT-23)