Editorial Volume 5, Issue 5 pp 332—334

Figure 1. Schematic diagram illustrating structural differences between the median eminence and ARH of mice fed ad libitum and fasting mice, and their effects on the diffusion of blood-borne signals into the brain. The arcuate nucleus of the hypothalamus (ARH) lies lateral to the third ventricle (3V) and immediately dorsolateral to the median eminence (ME). In mice fed normally (left half of the figure), the fenestrated blood vessels of the ME permit the local diffusion of macromolecules from the circulation, while vessels in the ARH proper exhibit blood-brain barrier properties that block this diffusion (not shown). Hence, circulating metabolic signals whose levels are high in the fed state (e.g., leptin and glucose) require BBB transport to access ARH neurons. Under these conditions, tight junctions (green) between tanycytes line the ventricular wall of the ME, preventing the diffusion of circulating factors into the 3V and CSF. During fasting or energy restriction (right half of the figure), the levels of hormones such as ghrelin rise, along with products of lipolysis (e.g., fatty acids), while leptin and glucose levels fall. Concomitantly, some ME vessels extending into the ARH become fenestrated, while the tight junction barrier along the 3V extends dorsally. These changes allow the freer diffusion of circulating signals that indicate energy restriction to ARH cells, including AgRP/NPY neurons that lie in the ventromedial ARH, while preventing the access of these substances to the rest of the brain through the CSF. The focal plasticity of this dual-faceted blood-hypothalamus barrier thus enhances the orexigenic/anabolic response to energy deficits.