Effects of Leptin and Neurotensin in Dorsal Motor Nucleus of the Vagus in Rats

• Main Authors: Tzu-Ling Li, 李紫鈴
• Other Authors: Ling-Ling Hwang, Ph D
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/11054868030544109486

碩士 === 臺北醫學大學 === 醫學研究所 === 91 === Obesity is one of the major public health problems in many countries in the world including Taiwan and is also a serious threat to health. Regulation of energy homeostasis is critical in body weight control. The hypothalamus, capable of detecting peripheral signals, and thus regulating energy intake (feeding) and expenditure by forming links between central and peripheral systems, appears to be the major integrating site of the adiposity signaling in the central nervous system (CNS). Evidences also suggest brain stem as an important structure involving in the regulation of energy balance. It has been shown that leptin is secreted in proportion to adiposity to serve as negative feedback signaling molecules on the regulation of body adiposity by acting in the hypothalamus. Neurotensin is a neurotransmitter known to be involved in energy homeostasis by reducing food intake. The receptors of leptin and neurotensin were found not only in the hypothalamus but also in the brain stem. Other anatomical evidences imply the dorsal motor nucleus of the vagus (DMNV) as a potential site of action for both leptin and neurotensin. By using whole-cell patch-clamp recording in brainstem slices, the effects of leptin and neurotensin were investigated in the present study. Leptin was found to either depolarize or hyperpolarize 19% and 15% of DMNV neurons, respectively, in a dose-dependent manner in the range of 0.5 nM to 300 nM. Neurotensin depolarize 52% of DMNV neurons. The effects of leptin and neurotensin persisted in the presence of tetrodotoxin, indicating direct effects of leptin and neurotensin on DMNV neurons. With the use of voltage-clamp recording techniques, the current-voltage (I-V) relationship of leptin- or neurotensin-induced currents were examined. Leptin-induced inward current exhibited a negative slope with a reversal potential of -87mV and the reversal potential was shift to -60mV in a high potassium Krebs solution. These results indicate that a decrease of potassium conductance may underlie leptin-induced inward current (or depolarization). Leptin-induced outward current exhibited a positive slope with a reversal potential of -85±3(n=4)mV implying that an increase of potassium conductance may be the major ionic mechanism of leptin-induced outward current (or hyperpolarization). Similar to the results of leptin-induced inward current a negative slope of the I-V curve and a reversal potential of -92±3mV(n=9) were obtained for neurotensin-induced inward current suggesting a decrease of potassium conductance as the underlying mechanism. By using retrograde labeling and intracellular staining techniques, the parasympathetic preganglionic neurons in the DMNV were identified. Our results show that leptin- and neurotensin-depolarized or hyperpolarized DMNV neurons include identified parasympathetic preganglionic neurons. The results suggest that DMNV is one of the target sites of leptin and neurotensin in the central nervous system and imply a role of leptin and neurotensin in the regulation of parasympathetic activity.