Age- and Sex-Specific Regulation of Serine Racemase in the Retina of an Alzheimer's Disease Mouse.
Wang Yan, Xu Dehuan, Zhao Yuhang, Zhu Haiyu, Xiu Xiaoyu, Jiang Haiyan, Liu Yimei, Shan Ge, Wu Shengzhou
AI Summary
This study found age- and sex-specific serine racemase changes in AD mouse retinas correlated with pathology, but occurred too late for early detection, suggesting use for staging or monitoring interventions.
Abstract
Purpose
Changes associated with Alzheimer's disease (AD) may have measurable effects on the retina, which may facilitate early detection due to the eye's accessibility. Retinal pathology and the regulation of serine racemase (SR) were investigated in the retinas of APP(SW)/PS1(∆E9) mice.
Methods
SR in the retinas and the content of D-serine in the aqueous humor were analyzed. The structure and function of the retina were assessed. Additionally, the regulation of SR in primary Müller cell cultures was investigated.
Results
SR levels were significantly higher in the retinas of 18- and 24-month-old male APP/PS1 mice, whereas aqueous humor D-serine was lower in 24-month-old APP/PS1 male mice compared to wild-type (WT) mice. Neither Aβ nor 17β-estradiol increased SR, but the combination of both did in Müller cell cultures. In contrast, 17β-estradiol increased Srr mRNA in the cultures. At 8 months of age, male APP/PS1 mice began to display reduced b-wave amplitude in scotopic and photopic electroretinography (ERG) recordings, unlike female APP/PS1 mice. Although the retinal layer thickness in APP/PS1 mice did not differ from WT mice, there was overt apoptosis in the inner and outer nuclear layers of the APP/PS1 mice retinas.
Conclusions
The age- and sex-specific regulation of SR is correlated with the pathology of an AD retina. Because the time window for SR regulation and D-serine alteration occurs after photoreceptor dysfunction in the AD retinas, it has limited value as a detection biomarker but may be useful as a topographic biomarker for staging severity and monitoring drug interventions in the eye or central nervous system.
MeSH Terms
Shields Classification
Key Concepts5
Serine racemase (SR) levels were significantly higher in the retinas of 18- and 24-month-old male APP/PS1 mice compared to wild-type (WT) mice.
Aqueous humor D-serine was lower in 24-month-old APP/PS1 male mice compared to wild-type (WT) mice.
Neither Aβ nor 17β-estradiol alone increased serine racemase (SR) levels, but the combination of both did in primary Müller cell cultures.
At 8 months of age, male APP/PS1 mice began to display reduced b-wave amplitude in scotopic and photopic electroretinography (ERG) recordings, unlike female APP/PS1 mice.
Overt apoptosis was observed in the inner and outer nuclear layers of the APP/PS1 mice retinas, despite no difference in retinal layer thickness compared to wild-type (WT) mice.
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