Fetuin‐A in the developing brain

Abstract

The serum protein fetuin-A is essential for mineral homeostasis and shows immunomodulatory functions, for example by binding to TGF superfamily proteins. It proved neuroprotective in a rat stroke model and reduced lethality after systemic lipopolysaccharide challenge in mice. Serum fetuin-A concentrations are highest during intrauterine life. Different species show intrauterine cerebral fetuin-A immunoreactivity, suggesting a contribution to brain development. We therefore aimed at specifying fetuin-A immunoreactivity in brains of newborn rats (age P0-P28) and human neonates (20-40 weeks of gestation). In humans and rats, fetuin-A was found in cortex, white matter, subplate, hippocampus, subventricular zone, and ependymal cells which supports a global role for brain function. In rats, overall fetuin-A immunoreactivity decreased with age. At P0 fetuin-A immunoreactivity affected most brain structures. Thereafter, it became increasingly restricted to distinct cells of the hippocampus, cingular gyrus, periventricular stem cell layer, and ependyma. In ependymal cells the staining pattern complied with active transependymal transport from cerebrospinal fluid. Double immunofluorescence studies revealed colocalization with NeuN (mature neurons), beta III tubulin (immature neurons), GFAP (astrocytes), and CD68 (activated microglia). This points to a role of fetuin-A in different brain functional systems. In human neonatal autopsy cases, frequently affected from severe neurological and non-neurological diseases, fetuin-A immunoreactivity was heterogeneous and much less associated with age than in healthy tissues studied earlier, suggesting an impact of exogeneous noxious factors on fetuin-A regulation. Further research on the role of fetuin-A in the neonatal brain during physiological and pathological conditions is recommended.

The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats

“…When up-regulated, the enzyme has been shown to increase the glycolytic pathway and decrease the pentose phosphate pathway, increasing oxidative stress, and apoptotic neuronal death [ 88 , 89 ]. Alpha-2-HS-glycoprotein, also known as fetuin-A (down-regulated; p < 0.0005), is a neuroprotective protein the function of which has been demonstrated in a rat stroke model [ 90 ] and in early brain ischemic injury, whereby it attenuates the brain inflammatory response [ 91 ]. It has also been shown to play a part in brain development [ 90 ].…”

“…Alpha-2-HS-glycoprotein, also known as fetuin-A (down-regulated; p < 0.0005), is a neuroprotective protein the function of which has been demonstrated in a rat stroke model [ 90 ] and in early brain ischemic injury, whereby it attenuates the brain inflammatory response [ 91 ]. It has also been shown to play a part in brain development [ 90 ]. Hence, the up-regulation of 6-phosphofructokinase type C and down-regulation of fetuin-A suggest an increased oxidative stress in the olfactory bulb, which may explain the increased neuronal cell death, as previously demonstrated by Deng et al [ 85 ].…”

Serum Antibody Biomarkers for ASD

“…After affinity purification of serum using the ASD1 peptoid, and observation of this analyte by Coomassie Blue staining after gel electrophoresis, we found a single band whose mass does not correspond with an antibody fragment. After sequencing this band, we identified two nonantibody proteins that were pulled down by the ASD1 peptoid: (1) Fetuin-A, a glycoprotein primarily involved in mineral homeostasis, has been suggested to play a neuroprotective role in the developing brain (Elsas et al, 2013). In addition, mutations in Fetuin-A's corresponding gene have recently been linked to a developmental disorder (3q27.3) exhibiting some autistic features (Thevenon et al, 2014).…”

Fetuin-A protein distribution in mature inflamed and ischemic brain tissue

“…The distribution of fetuin-A in the developing brain was examined in various species. In the developing neocortex fetuin-A co-localized with a population of cells that migrated from the ventricular zone to form the primordial plexiform layer and the early cortical plate [ 17 , 20 – 23 ]. Dziegielewska and colleagues [ 22 ] observed that the distribution of fetuin-A in the early cortical plate of human embryos of 7 weeks and sheep embryos of 35–36 days was very similar.…”

“…In human fetuses of 33 weeks of gestational age, fetuin-A staining was negative. Previously, we examined the distribution of fetuin-A in the brain of human and rat fetuses and in newborns [ 23 ]. In human tissue, fetuin-A staining decreased with age, but still was found in the cortex of term born neonates.…”