Dietary Impact on Neuronal Autophagy Control and Brain Health

Feed Your Mind - How Does Nutrition Modulate Brain Function throughout Life? ◽

10.5772/intechopen.85228 ◽

2019 ◽

Author(s):

Claudia Ntsapi ◽

Andre du Toit ◽

Ben Loos

Keyword(s):

Brain Health ◽

Neuronal Autophagy

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Neurodegeneration Caused by S1P-Lyase Deficiency Involves Calcium-Dependent Tau Pathology and Abnormal Histone Acetylation

Cells ◽

10.3390/cells9102189 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2189 ◽

Cited By ~ 1

Author(s):

Shah Alam ◽

Antonia Piazzesi ◽

Mariam Abd El Fatah ◽

Maren Raucamp ◽

Gerhild van Echten-Deckert

Keyword(s):

Histone Acetylation ◽

Brain Health ◽

Gene Encoding ◽

Calcium Dependent ◽

Sphingosine Kinase 2 ◽

Calcium Chelation ◽

Sphingosine 1 Phosphate ◽

S1p Lyase ◽

The Brain ◽

Neuronal Autophagy

We have shown that sphingosine 1-phosphate (S1P) generated by sphingosine kinase 2 (SK2) is toxic in neurons lacking S1P-lyase (SGPL1), the enzyme that catalyzes its irreversible cleavage. Interestingly, patients harboring mutations in the gene encoding this enzyme (SGPL1) often present with neurological pathologies. Studies in a mouse model with a developmental neural-specific ablation of SGPL1 (SGPL1fl/fl/Nes) confirmed the importance of S1P metabolism for the presynaptic architecture and neuronal autophagy, known to be essential for brain health. We now investigated in SGPL1-deficient murine brains two other factors involved in neurodegenerative processes, namely tau phosphorylation and histone acetylation. In hippocampal and cortical slices SGPL1 deficiency and hence S1P accumulation are accompanied by hyperphosphorylation of tau and an elevated acetylation of histone3 (H3) and histone4 (H4). Calcium chelation with BAPTA-AM rescued both tau hyperphosphorylation and histone acetylation, designating calcium as an essential mediator of these (patho)physiological functions of S1P in the brain. Studies in primary cultured neurons and astrocytes derived from SGPL1fl/fl/Nes mice revealed hyperphosphorylated tau only in SGPL1-deficient neurons and increased histone acetylation only in SGPL1-deficient astrocytes. Both could be reversed to control values with BAPTA-AM, indicating the close interdependence of S1P metabolism, calcium homeostasis, and brain health.

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