Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Abstract

Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.

Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct G-protein-coupled receptors and signaling cascades

“…The 18:1 LPE stimulates chemotactic migration and cellular invasion in SK-OV3 human ovarian cancer cells [10] and cell proliferation of human MDA-MB-231 breast cancer cells [11]. Egg yolk LPE stimulates differentiation and maturation of mouse astrocyte in culture [12]. Thus, LPE evokes various response, depending on the cell type.…”

“…Extracellularly, LPE has been detected in human serum at levels of several hundred nanograms per milliliter, but its physiological role remains largely unknown [8]. A few studies suggest the cell-type speci c roles of LPE in cultures [9][10][11][12]. Interestingly, several studies show that cognitive impairment or traumatic brain damage in rodent model is accompanied by changes in LPE revels in the brain [13][14][15], suggesting the physiological or pathological signi cance of LPE.…”

Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct signaling pathway

“…The 18:1 LPE stimulates chemotactic migration and cellular invasion in SK-OV3 human ovarian cancer cells [19] and cell proliferation of MDA-MB-231 breast cancer cells [20]. Egg yolk LPE stimulates differentiation and maturation of mouse astrocyte in culture [21]. Thus, LPE evokes various response, depending on the cell type.…”

“…Extracellularly, LPE has been detected in human serum at levels of several hundred nanograms per milliliter [17], but its physiological role remains largely unknown. A few studies suggest the cell-type speci c roles of LPE in cultures [18][19][20][21]. Interestingly, several studies show that cognitive impairment or traumatic brain damage in rodent model is accompanied by changes in LPE revels in the brain [22][23][24].…”

Effect of Inflammatory Stress on Neural Stem Cells Behaviour: A Rescue Effect of Phosphatidylcholine by Modulating Neuronal Plasticity.

“…We have previously demonstrated that phospholipids affect the fate of post-mitotic neural precursors; speci cally, phosphatidylcholine (PtdCho) promotes neuronal differentiation at expenses of astroglial and unspeci ed precursors 15 . As the loss of neurons is the detrimental outcome of brain injuries and neurodegenerative diseases, we asked whether PtdCho could still favour neuronal differentiation under in ammatory conditions, and thus prevent or restore tissue damage in this context.…”