LMO4 Is Essential for Paraventricular Hypothalamic Neuronal Activity and Calcium Channel Expression to Prevent Hyperphagia
| Autor: | Kianoosh Keyhanian, Kendall Wen, Hsiao-Huei Chen, Nihar R. Pandey, Tariq Zaman, Alexandre F.R. Stewart, Xun Zhou, Ryan D Courtney, Zhaohong Qin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Transgene Mice Transgenic Calcium Channels R-Type Hyperphagia Biology Calcium Channels T-Type Eating Mice Slice preparation Internal medicine medicine Animals Humans Premovement neuronal activity Receptor Cation Transport Proteins Adaptor Proteins Signal Transducing Mice Knockout Neurons Voltage-dependent calcium channel General Neuroscience Calcium channel digestive oral and skin physiology Articles LIM Domain Proteins Mice Inbred C57BL Endocrinology Gene Expression Regulation Hypothalamus Calcium Channels Neuroscience Homeostasis Paraventricular Hypothalamic Nucleus |
| Zdroj: | The Journal of Neuroscience. 34:140-148 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3419-13.2014 |
| Popis: | The dramatic increase in the prevalence of obesity reflects a lack of progress in combating one of the most serious health problems of this century. Recent studies have improved our understanding of the appetitive network by focusing on the paraventricular hypothalamus (PVH), a key region responsible for the homeostatic balance of food intake. Here we show that mice with PVH-specific ablation of LIM domain only 4 (Lmo4) become rapidly obese when fed regular chow due to hyperphagia rather than to reduced energy expenditure. Brain slice recording of LMO4-deficient PVH neurons showed reduced basal cellular excitability together with reduced voltage-activated Ca2+currents. Real-time PCR quantification revealed that LMO4 regulates the expression of Ca2+channels (Cacna1h,Cacna1e) that underlie neuronal excitability. By increasing neuronal activity using designer receptors exclusively activated by designer drugs technology, we could suppress food intake of PVH-specific LMO4-deficient mice. Together, these results demonstrate that reduced neural activity in LMO4-deficient PVH neurons accounts for hyperphagia. Thus, maintaining PVH activity is important to prevent hyperphagia-induced obesity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|