Hypothalamic BDNF gene expression is modulated by thyroid hormones in vivo.

Abstract

Brain-derived neurotrophic factor (BDNF) has been implicated in the etiology of human eating disorders, specifically obesity and anorexia, with mature-onset obesity being induced by hyperphagia. Endocrine abnormalities often interact with hypothalamic pathways to induce alterations in food intake and/or body weight. Therefore, we sought to investigate whether thyroid hormone could modulate hypothalamic BDNF gene expression in vivo. First, we injected chicken embryos on embryonic day e18 and e19 with 0.1 ml of 10 −9 M T 3 , 0.075 g/mL methimazole (a thyroid hormone synthesis inhibitor) or a similar volume of water and then collected the hypothalami on e20. Decreased BDNF and thyrotropin-releasing hormone (TRH) mRNA levels were observed in the T 3 relative to methimazole-treated hypothalami using quantitative real-time PCR (qPCR) measurements ( P n =6). Next, we determined whether T 3 inhibited BDNF expression in juvenile chickens surgically implanted at 29 days of age with osmotic minipumps that delivered 192 μg T 3 /kg/day ( n =5) or 50% DMSO/50% propylene glycol as vehicle control (VC) ( n =4). After 3 days of treatment, exogenous T 3 suppressed hypothalamic BDNF and TRH gene expression relative to VC animals ( P 3 alters hypothalamic BDNF expression in vivo, which could influence the neural circuitry controlling the anorexic or obese phenotype. Hyperthyroidism decreases BDNF expression, which could lead to hyperphagia to support increased metabolism. This interaction is a potential homeostatic mechanism that links hypothalamic energy regulation with food intake and body weight.