Amyloid-β Processing in Aged S100B Transgenic Mice Is Sex Dependent.

Krista Minéia Wartchow,Carlos-Alberto Gonçalves,Leticia Rodrigues,Michael Buchfelder,Izabela Swierzy,Andrea Kleindienst,Diogo Onofre De Souza

doi:10.3390/ijms221910823

Krista Minéia Wartchow, Carlos-Alberto Gonçalves + Show 5 more

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https://doi.org/10.3390/ijms221910823

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Abstract

(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-β 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-β 42 (Aβ42) 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 Aβ immunostaining were performed for visualization of Aβ deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aβ42 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 Aβ immunostaining demonstrated Aβ 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 Aβ processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.

Highlights

Calcium-binding protein S100B is most abundant in brain tissue, mainly expressed and secreted by astrocytes [1], and exerts dose-dependent either neurotrophic or neurotoxic effects
Since the dorsal hippocampus is especially susceptible to neurodegeneration [48], and amyloid-β 42 (Aβ42) staining in our series suggested an amyloid aggregation in the hilus of the hippocampus, we evaluated the Thioflavin T (ThT) staining of different dorsal hippocampal pathways but could not verify any regional differences, neither in wt nor in S100Btg mice
S100B levels in the adipose tissue, the model is distinguished for exploring central nervous system diseases, where cerebrospinal fluid (CSF) and serum measurements are relevant

Summary

Introduction

Calcium-binding protein S100B is most abundant in brain tissue, mainly expressed and secreted by astrocytes [1], and exerts dose-dependent either neurotrophic or neurotoxic effects (for review, see [2]). Extracellular S100B levels have been proposed as a marker of brain injury, in blood [3] and cerebrospinal fluid (CSF) [3,4]. One potential contributor to increased S100B serum levels is the adipose tissue since adipocytes express S100B [5]. Whether the increase in S100B in neurodegenerative diseases is part of a compensatory response, contributes to the pathology, or results from dysregulated feedback loops has not been clarified yet. The therapeutic short-term increase in S100B levels promoted hippocampal neurogenesis in rodents, even following experimental brain injury [10,11]

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