ABSTRACT
(1) The neurotrophic protein S100B is a marker of brain injury and has been associated with neuroregeneration. In S100Btg mice rendering 12 copies of the murine S100B gene we evaluated whether S100B may serve as a treatment option. (2) In juvenile, adult, and one-year-old S100Btg mice (female and male; n = 8 per group), progenitor cell proliferation was quantified in the subgranular zone (SGZ) and the granular cell layer (GCL) of the dentate gyrus with the proliferative marker Ki67 and BrdU (50 mg/kg). Concomitant signaling was quantified utilizing glial fibrillary acidic protein (GFAP), apolipoprotein E (ApoE), brain-derived neurotrophic factor (BDNF), and the receptor for advanced glycation end products (RAGE) immunohistochemistry. (3) Progenitor cell proliferation in the SGZ and migration to the GCL was enhanced. Hippocampal GFAP was reduced in one-year-old S100Btg mice. ApoE in the hippocampus and frontal cortex of male and BDNF in the frontal cortex of female S100Btg mice was reduced. RAGE was not affected. (4) Enhanced hippocampal neurogenesis in S100Btg mice was not accompanied by reactive astrogliosis. Sex- and brain region-specific variations of ApoE and BDNF require further elucidations. Our data reinforce the importance of this S100Btg model in evaluating the role of S100B in neuroregenerative medicine.
Subject(s)
Brain-Derived Neurotrophic Factor , Hippocampus , Animals , Apolipoproteins E/metabolism , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cell Proliferation , Disease Models, Animal , Female , Hippocampus/metabolism , Male , Mice , Mice, Transgenic , Neurogenesis , S100 Calcium Binding Protein beta Subunit/genetics , S100 Calcium Binding Protein beta Subunit/metabolismABSTRACT
(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-ß processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-ß 42 (Aß42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aß immunostaining were performed for visualization of Aß deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aß42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aß immunostaining demonstrated Aß deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aß processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.
Subject(s)
Adipose Tissue/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Brain/metabolism , Hippocampus/metabolism , Protein Processing, Post-Translational , S100 Calcium Binding Protein beta Subunit/metabolism , Alzheimer Disease/metabolism , Animals , Female , Male , Mice , Mice, Transgenic , S100 Calcium Binding Protein beta Subunit/genetics , Sex FactorsABSTRACT
The clinical significance of serum S-100ß levels in neonates with hypoxic-ischemic encephalopathy (HIE), as a reference index to assess HIE severity, was evaluated in this study. On the basis of our strict inclusion and exclusion criteria, relevant high-quality case-control studies reporting the association between HIE and S-100ß protein were selected from electronic database searches. The STATA version 12.0 software was used for the statistical analyses. The database search initially retrieved 93 studies (37 in English and 56 in Chinese), and following a multistep screening process, 13 high-quality studies were eventually included in our meta-analysis. The 13 case-control studies included a total of 646 HIE neonates and 381 healthy controls. The results of this meta-analysis revealed that serum S-100ß levels in mild, moderate, and severe HIE neonates were significantly higher than those in healthy controls, and the differences were statistically significant. Importantly, the serum S-100ß levels increased incrementally with HIE severity. Our results support the hypothesis that S-100ß is an important biological indicator of HIE and serum S-100ß levels can be used as a reference index to assess HIE severity.