No abstract

Astrocytes appear star-shaped in the brain, increasingly so after injury. When astroglia are cultured in serum-containing medium, they exhibit a flat, fibroblast-like morphology. In serum-free medium, astrocytes become stellate, with many long processes. The serine protease alpha-thrombin mimics the effects of serum at subnanomolar concentrations, whereas the thrombin-inhibiting serpin, protease nexin I (PNI), reverses the thrombin effect. In our current experiments, murine neonatal spinal cord astrocytes became stellate after 4 hr in serum-free medium, while cortical astrocytes required 12 hr in serum-free medium for stellation. Astrocytes from either region flattened after 60 min in medium containing 3.0 to 300 pM proteolytically active human alpha-thrombin. After 12 hr in thrombin-containing medium, 98% of the astrocytes had a flattened morphology. No flattening occurred if alpha-thrombin was replaced by gamma-thrombin, which has its fibrinogen-recognition exosite disrupted. PNI added at 1 nM to serum-containing medium caused stellation after 3 hr, and astroglia were 50% stellate by 12 hr. The effect of thrombin was mimicked by a 7-amino acid peptide (TRP-7) from the cleavage site of the human thrombin receptor. This peptide caused 40% of the astrocytes in serum-free medium to exhibit a flattened morphology after 6 hr. PNI had no effect on TRP-7 action on astrocytes. These results indicate that astrocytes possess a cell-surface receptor for thrombin, similar to that described for platelets, endothelial cells, and neurons.

Sugar has become embedded in modern food and beverages. This has led to overconsumption of sugar in children, adolescents, and adults, with more than 60 countries consuming more than four times (>100 g/person/day) the WHO recommendations (25 g/person/day). Recent evidence suggests that obesity and impulsivity from poor dietary habits leads to further overconsumption of processed food and beverages. The long-term effects on cognitive processes and hyperactivity from sugar overconsumption, beginning at adolescence are not known. Using a well-validated mouse model of sugar consumption, we found that long-term sugar consumption, at a level that significantly augments weight gain, elicits an abnormal hyperlocomotor response to novelty and alters both episodic and spatial memory. Our results are similar to those reported in attention deficit and hyperactivity disorders. The deficits in hippocampal-dependent learning and memory were accompanied by altered hippocampal neurogenesis, with an overall decrease in the proliferation and differentiation of newborn neurons within the dentate gyrus. This suggests that long-term overconsumption of sugar, as that which occurs in the Western Diet might contribute to an increased risk of developing persistent hyperactivity and neurocognitive deficits in adulthood.