Uptake of Exogenous Aspartate into Circumventricular Organs but Not Other Regions of Adult Mouse Brain

Adult mice were treated intraperitoneally with aspartate (Asp) at one of several doses (0.47–3.75 mmol/kg) and 30 min later given a subcutaneous Asp injection at the same dose. This treatment regimen resulted in steady state blood Asp elevations, a given dose producing the same degree of elevation at both 30 and 60 min. The lowest and highest doses, respectively, produced fourfold and 55‐fold elevations of serum Asp. In selected circumventricular organ (CVO) regions of brain which lack blood brain barriers, tissue Asp levels rose 1.5 and 3 times above control values following the lowest and highest doses, respectively, whereas tissue Asp remained unchanged in non‐CVO brain regions. Thus, even very moderate Asp dosing causes marked increases in CVO Asp. In order to analyze the pattern of Asp uptake into CVO, Asp was assayed in numerous subdivisions of each CVO, and maps were constructed which reflected microregional concentration differences. The pattern of Asp distribution suggests that Asp enters brain via fenestrated capillaries serving certain portions of CVO and then spreads into adjacent brain tissue. In separate experiments, we administered a single high dose of Asp (15 mmol/kg) to both adult and infant mice and measured Asp in serum and select brain regions 60 min later. Asp concentrations in serum and CVO (but not other brain regions) rose markedly at both ages but the increases were greater in serum and therefore also in CVO of infants. This may explain in part the observation that a given dose of Asp destroys a larger number of CVO neurons in infant than in adult mice. Our findings support a growing body of evidence that CVO are an important communication link between blood and brain.