Palmitic acid, but not other long-chain saturated fatty acids, increases S100B protein and TNF-α secretion by astrocytes.

Obesity is a health problem that involves fat accumulation in adipose and other tissues and causes cell dysfunction. Long-chain saturated fatty acids can induce and propagate inflammation, which may also contribute to the brain alterations found in individuals with obesity. Fatty acids accumulate in astrocytes in situations of blood‒brain barrier disruption, such as inflammatory conditions. Furthermore, the increase in tumor necrosis factor-alpha (TNF-α) and S100 calcium-binding protein B (S100B) secretion is considered an essential component of the inflammatory response. We hypothesize that through their action on astrocytes, long-chain saturated fatty acids mediate some of the brain alterations observed in individuals with obesity. Here, we investigate the direct effect of long-chain fatty acids on astrocytes. Primary astrocyte cultures were incubated for 24 hours with myristic, palmitic, stearic, linoleic, or α-linolenic acids (25-100 µM). All saturated fatty acids tested led to an increase in TNF-α secretion, but only palmitic acid, one of the most common fatty acids, increased S100B secretion, indicating that S100B secretion is probably not caused in response to TNF-α release. Palmitic acid also caused nuclear migration of nuclear factor kappa B. Long-chain saturated fatty acids did not alter cell viability or redox status. In conclusion, long-chain saturated fatty acids can alter astrocytic homeostasis and may contribute to brain disorders associated with obesity, such as neuroinflammation.

Effect of senescence on the tyrosine hydroxylase and S100B immunoreactivity in the nigrostriatal pathway of the rat.

Senescence is a natural and progressive physiological event that leads to a series of morphophysiological alterations in the organism. The brain is the most vulnerable organ to both structural and functional changes during this process. Dopamine is a key neurotransmitter for the proper functioning of the brain, directly involved in circuitries related with emotions, learning, motivation and reward. One of the main dopamine- producing nuclei is the substantia nigra pars compacta (SNpc), which establish connections with the striatum forming the so-called nigrostriatal pathway. S100B is a calcium binding protein mainly expressed by astrocytes, involved in both intracellular and extracellular processes, and whose expression is increased following injury in the nervous tissue, being a useful marker in altered status of central nervous system. The present study aimed to analyze the impact of senescence on the cells immunoreactive for tyrosine hydroxylase (TH) and S100B along the nigrostriatal pathway of the rat. Our results show an decreased expression of S100B+ cells in SNpc. In addition, there was a significant decrease in TH immunoreactivity in both projection fibers and TH+ cell bodies. In the striatum, a decrease in TH immunoreactivity was also observed, as well as an enlargement of the white matter bundles. Our findings point out that senescence is related to the anatomical and neurochemical changes observed throughout the nigrostriatal pathway.

Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.