Role of the blood-brain barrier in the evolution of feeding and cognition

Abstract

The blood-brain barrier (BBB) regulates the blood-to-brain passage of gastrointestinal hormones, thus informing the brain about feeding and nutritional status. Disruption of this communication results in dysregulation of feeding and body weight control. Leptin, which crosses the BBB to inform the CNS about adiposity, provides an example. Impaired leptin transport, especially coupled with central resistance, results in obesity. Various substances/conditions regulate leptin BBB transport. For example, triglycerides inhibit leptin transport. This may represent an evolutionary adaptation in that hypertriglyceridemia occurs during starvation. Inhibition of leptin, an anorectic, during starvation could have survival advantages. The large number of other substances that influence feeding is explained by the complexity of feeding. This complexity includes cognitive aspects; animals in the wild are faced with cost/benefit analyses to feed in the safest, most economical way. This cognitive aspect partially explains why so many feeding substances affect neurogenesis, neuroprotection, and cognition. The relation between triglycerides and cognition may be partially mediated through triglyceride's ability to regulate the BBB transport of cognitively active gastrointestinal hormones such as leptin, insulin, and ghrelin.

Figure 1

Relation between vascular and CNS levels of leptin. CSF versus blood levels of leptin (open circles, dotted line) are derived from several studies of humans in the literature.– Brain versus vascular levels of leptin (solid circle, solid line) are derived from a brain perfusion study. Either approach shows a hyperparabolic relation between CNS and vascular levels of leptin that is explained by the saturable nature of the blood-to-brain transport of leptin across the BBB. With either approach, the curve shows significant saturation at relatively low vascular levels of leptin.