Accumulating evidence suggests the possible association between the concentrations of serum brain-derived neurotrophic factor (BDNF) and psychiatric disease with impaired brain development. Yet the reasons remain unclear. We therefore investigated the characteristics of serum BDNF as well as its age-related changes in healthy controls in comparison to autism cases. BDNF was gradually released from platelets at 4 degrees C, reached a maximal concentration after around 24 h, and remained stable until 42 h. At room temperature, BDNF was found to be immediately degraded. Circadian changes, but not seasonal changes, were found in serum levels of BDNF existing as the mature form with a molecular mass of 14 kDa. In healthy controls, the serum BDNF concentration increased over the first several years, then slightly decreased after reaching the adult level. There were no sex differences between males and females. In the autism cases, mean levels were significantly lower in children 0-9 years old compared to teenagers or adults, or to age-matched healthy controls, indicating a delayed BDNF increase with development. In a separate study of adult rats, a circadian change in serum BDNF was found to be similar to that in the cortex, indicating a possible association with cortical functions.

We previously demonstrated that human hepatocellular carcinoma-derived HuH-7 cells stimulated with interleukin1b (IL-1b) produce a 1 -acid glycoprotein (AGP) with increased amounts of sialyl Lewis X (sLeX) antigen, although the mechanism remained obscure. Here, we report our investigation of the mechanism. sLeX expression on HuH-7 cells was induced 2.5 times more after 48 h stimulation with 100 U/mL IL-1b compared with control, as indicated by anti-sLeX antibody binding. Furthermore, expression of 2,3-sialylated N-acetyllactosamine increased gradually up to 48 h after IL-1b stimulation; this preceded the increase in sLeX expression. Increases in a2,3-sialyltransferase activity also preceded increases in a1,3-fucosyltransferase activity. Furthermore, mRNA levels of ST3Gal IV, FUT IV and VI in HuH-7 cells stimulated with IL-1b were increased at 2-4 h, while increases in FUT VI mRNA level occurred gradually after 24 h. IL-1b-induced sLeX expression on HuH-7 cells was suppressed by transfection of gene-specific small interference RNAs against FUT VI and ST3Gal IV but not against FUT IV and ST3Gal III. These data results that IL-1b induces expression of sLeX on HuH-7 cells by enhanced expression of FUT VI and ST3Gal IV gene.

Circadian variation in the expression of brain‐derived neurotrophic factor (BDNF) indicates that BDNF is involved in the regulation of diurnal rhythms in a variety of biological processes. However, it is still unclear which brain regions alter their BDNF levels in response to external light input. Therefore, in selected brain regions of adult male rats, we investigated diurnal variation, as well as the effects of a single eight‐hour phase advance of the light‐dark cycle, on the levels of BDNF and of other neurotrophins. The cerebellum, hippocampus and cerebral cortex containing visual cortex (VCX) showed diurnal variation in BDNF protein levels and the VCX also in NT‐3 levels. In the VCX and the region containing the entorhinal cortex and amygdala (ECX), BDNF protein levels were increased 12 h after the phase advance, while BDNF mRNA levels were increased significantly in the VCX and slightly in the ECX after 4 h. After one week, however, BDNF protein levels were reduced in eight brain regions out of 13 examined. BDNF levels in the ECX and VCX were significantly different between light rearing and dark rearing, while a hypothyroid status did not produce an effect. Cyclic AMP responsive element‐binding protein (CREB), a transcription factor for BDNF, was greatly activated by the phase advance in the ECX and VCX, suggesting the existence of CREB‐mediated pathways of BDNF synthesis that are responsive to external light input.

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