Biosynthesis of Astrocytic Trehalose Regulates Neuronal Arborization in Hippocampal Neurons

Trehalose is a nonreducing disaccharide that has recently attracted much attention because of its ability to inhibit protein aggregation, induce autophagy, and protect against dissections and strokes. In vertebrates, the biosynthesis of trehalose was long considered absent due to the lack of annotated genes involved in this process. In contrast, trehalase (TreH), which is an enzyme required for the cleavage of trehalose, is known to be conserved and expressed. Here, we show that trehalose is present as an endogenous metabolite in the rodent hippocampus. We found that primary astrocytes were able to synthesize trehalose and release it into the extracellular space. Notably, the TreH enzyme was observed only in the soma of neurons, which are the exclusive users of this substrate. A statistical analysis of the metabolome during different stages of maturation indicated that this metabolite is implicated in neuronal maturation. A morphological analysis of primary neurons confirmed that trehalose is required for neuronal arborization

Biosynthesis of Astrocytic Trehalose Regulates Neuronal Arborization in Hippocampal Neurons

Trehalose is a nonreducing disaccharide that has recently attracted much attention because of its ability to inhibit protein aggregation, induce autophagy, and protect against dissections and strokes. In vertebrates, the biosynthesis of trehalose was long considered absent due to the lack of annotated genes involved in this process. In contrast, trehalase (TreH), which is an enzyme required for the cleavage of trehalose, is known to be conserved and expressed. Here, we show that trehalose is present as an endogenous metabolite in the rodent hippocampus. We found that primary astrocytes were able to synthesize trehalose and release it into the extracellular space. Notably, the TreH enzyme was observed only in the soma of neurons, which are the exclusive users of this substrate. A statistical analysis of the metabolome during different stages of maturation indicated that this metabolite is implicated in neuronal maturation. A morphological analysis of primary neurons confirmed that trehalose is required for neuronal arborization

HRs and 95% CIs of breast cancer by HER2 status in relation to quartiles of B vitamin intake in ORDET women.

<p>* Adjusted for height, waist-hip-ratio, age at menarche, menopausal status, oral contraceptive use, parity, education, family history of breast cancer, energy intake, and alcohol intake.</p><p>** Tests for linear trend were calculated by assigning an ordinal number to each quartile.</p><p># HR of developing breast cancer per 1 SD increase in vitamin intake.</p><p>## HER2+ vs. HER2-.</p><p>HRs and 95% CIs of breast cancer by HER2 status in relation to quartiles of B vitamin intake in ORDET women.</p

HRs (95% CIs) of breast cancer in relation to quartiles of B vitamin intake in ORDET women.

<p>* Adjusted by energy intake.</p><p>** Adjusted by height, waist hip ratio, age at menarche, menopausal status, oral contraceptive use, parity, education, family history of breast cancer, energy intake and alcohol intake.</p><p># Tests for linear trend were calculated by assigning an ordinal number to each quartile.</p><p>## HR of developing breast cancer per 1 SD increase in vitamin intake</p><p>HRs (95% CIs) of breast cancer in relation to quartiles of B vitamin intake in ORDET women.</p

HRs (95% CIs) of breast cancer by ER plus PR status in relation to quartiles of B vitamin intake in ORDET women.

<p>* Adjusted for height, waist-hip-ratio, age at menarche, menopausal status, oral contraceptive use, parity, education, family history of breast cancer, energy intake, and alcohol intake.</p><p>** Tests for linear trend were calculated by assigning an ordinal number to each quartile.</p><p># HR of developing breast cancer per 1 SD increase in vitamin intake.</p><p>## ER+PR+ vs. ER-PR-</p><p>HRs (95% CIs) of breast cancer by ER plus PR status in relation to quartiles of B vitamin intake in ORDET women.</p

Baseline distribution of nutrients and factors influencing breast cancer risk by disease status in ORDET women.

<p>* SD = standard deviation</p><p>Baseline distribution of nutrients and factors influencing breast cancer risk by disease status in ORDET women.</p

Additional file 1: of Cross-sectional and longitudinal associations between energy intake and BMI z-score in European children

Baseline and follow-up characteristics (mean and SD) of exposure and outcome variates given by sex and age group at baseline for MVPA-subgroup. (DOCX 21 kb

Characteristic of subjects showing occult HCV.

*<p>: −/− indicates normal values below 50 IU/L and 35 IU/L for men and women respectively for ALT, and below 40 IU/L and 32 IU/L for men and women respectively for AST determination.</p><p>n.d.: the amplification resulting in a very weak fragment and sequence analysis did not succeed.</p

Hazard ratios (HRs) for developing breast cancer in relation to metabolic syndrome components.

<p>¹Stratified by age (5-year classes) and centre.</p><p>²Adjusted for menopausal status (whole cohort model only), number of full-term pregnancies, age at menarche, smoking status, education, physical activity, and alcohol intake; stratified by age (5-year classes) and centre.</p><p>³P for interaction between metabolic syndrome components and menopausal status.</p><p>Hazard ratios (HRs) for developing breast cancer in relation to metabolic syndrome components.</p

Baseline characteristics of the subcohort according to presence or absence of metabolic syndrome.

<p>Baseline characteristics of the subcohort according to presence or absence of metabolic syndrome.</p