Investigating the Role of Lactate in Regulating Gene Expression through Epigenetic Modifications in Neuronal Cells

الموضوعات

علوم تطبيقية وتكنولوجية

الملخص

Lactate has been long thought of as a dead-end waste product of glycolysis. In the brain,recent evidence has revealed a key role of L-lactate creating a paradigm-shift in ourunderstanding of the neuronal energy metabolism. The Astrocyte neuron lactate shuttle(ANLS) model, has shown L-Lactate as the main energy substrate delivered by astrocytesto neurons to sustain neuronal oxidative metabolism. This metabolic coupling is anessential mechanism for long-term memory formation. Experimental evidence indicatesthat the role of lactate in cognitive function is not limited to being a neuronal metabolicsubstrate, but rather it is also an important signaling molecule for synaptic plasticity. Oneof the new emerging roles of lactate is its effect on gene expression levels; however, ourcurrent understanding of the mechanism of lactate effect on gene expression isrudimentary. Here, I investigate the role of lactate as an epigenetic modulator in neuronalcultures. First, I explored the effect of lactate on the transcriptome and methylome of theneuronal cells using primary neuronal cell culture models. Our results reveal a significantrole for lactate in inducing neuronal cell differentiation. Following, I characterized aneuroblastoma cell line as our neuronal differentiation cell model and assessed itsmetabolic features relative to other immortal cell lines. Further, using the cell line in vitromodel, I looked into the metabolic reprograming that occurs in parallel with the firstindications of differentiation, focusing on lactate production rates. Subsequently, Iinvestigated the role of lactate in differentiation through transcriptomic analysis. We showthat lactate induced histone acetylation and promoted expression of dopaminergic markers,with a stronger effect of D-lactate over L-lactate. Further studies to establish potentiallinkages between those two pathways will enhance our understanding of the effect oflactate.

روابط وملفات

التعريف والنوع

رقم الوثيقة

021a4c58-80e5-47c4-8c53-f88f94d30389

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل دكتوراة

نوع الملف

pdf text

أسماء الملفات

2021472_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":"Hubert Fiumelli ","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"Manar Majdi Darwish","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"Pierre Magistretti","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

English

المصدر والدورية

اسم المصدر

Investigating the Role of Lactate in Regulating Gene Expression through Epigenetic Modifications in Neuronal Cells

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

Hubert Fiumelli , Pierre Magistretti

الإعداد

Manar Majdi Darwish

الاقتباسات الببليوغرافية